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Semaglutide

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Mar.28.2024

Semaglutide

Indications/Dosage

Labeled

  • obesity
  • reduction of cardiovascular mortality
  • type 2 diabetes mellitus
  • weight management

Off-Label

    † Off-label indication

    For the treatment of type 2 diabetes mellitus as an adjunct to diet and exercise

    Oral dosage (semaglutide-naive) (e.g., Rybelsus)

    Adults

    3 mg PO once daily for 30 days, then 7 mg PO once daily, initially. May increase the dose to 14 mg PO once daily after at least 30 days on 7 mg/day if additional glycemic control is needed. Administering two 7 mg tablets to achieve a 14 mg dose is not recommended.[64637]

    Oral dosage (converting from semaglutide injection) (e.g., Rybelsus)

    Adults

    7 or 14 mg PO once daily for 0.5 mg subcutaneously once weekly starting up to 7 days after the last injection. There is no equivalent oral dose for a 1 mg subcutaneous dose.[64637]

    Subcutaneous dosage (semaglutide-naive) (e.g., Ozempic)

    Adults

    0.25 mg subcutaneously once weekly for 4 weeks, then 0.5 mg subcutaneously once weekly, initially. May increase the dose to 1 mg subcutaneously once weekly after 4 weeks on 0.5 mg/week and 2 mg subcutaneously once weekly after 4 weeks on 1 mg/week if additional glycemic control is needed.[62656]

    Subcutaneous dosage (converting from semaglutide tablets) (e.g., Ozempic)

    Adults

    0.5 mg subcutaneously once weekly for 14 mg PO once daily starting the day after the last oral dose. There is no equivalent oral dose for a 1 mg subcutaneous dose.[64637]

    For the reduction of risk of major adverse cardiovascular events, including reduction of cardiovascular mortality, non-fatal myocardial infarction, or non-fatal stroke, in adults with established cardiovascular disease and type 2 diabetes mellitus or who are obese or overweight

    For reduction of risk of major cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease

    Subcutaneous dosage (Ozempic)

    Adults

    0.25 mg subcutaneously once weekly for 4 weeks, then 0.5 mg subcutaneously once weekly, initially. May increase the dose to 1 mg subcutaneously once weekly after 4 weeks on 0.5 mg/week and 2 mg subcutaneously once weekly after 4 weeks on 1 mg/week if additional glycemic control is needed.[62656]

    For reduction of risk of major cardiovascular events in adults with established cardiovascular disease and who are obese or overweight

    Subcutaneous dosage (Wegovy)

    Adults

    0.25 mg subcutaneously once weekly for weeks 1 through 4, then 0.5 mg subcutaneously once weekly for weeks 5 through 8, then 1 mg subcutaneously once weekly for weeks 9 through 12, then 1.7 mg subcutaneously once weekly for weeks 13 through 16. From week 17 and onward, a maintenance dose of 2.4 mg (recommended) or 1.7 mg subcutaneously once weekly. Consider delaying dose escalation for 4 weeks if a dose increase is not tolerated. Assess treatment response and tolerability when selecting the maintenance dose.[66713]

    For the treatment of obesity and for chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity

    NOTE: Semaglutide is indicated in adults with an initial body mass index (BMI) of 30 kg/m2 or more or 27 kg/m2 or more in the presence of other risk factors (e.g., hypertension, type 2 diabetes, or dyslipidemia) and pediatric patients age 12 years and older with an initial BMI at the 95th percentile or more for age and sex.[66713]

    Subcutaneous dosage (e.g., Wegovy)

    Adults

    0.25 mg subcutaneously once weekly for weeks 1 through 4, then 0.5 mg subcutaneously once weekly for weeks 5 through 8, then 1 mg subcutaneously once weekly for weeks 9 through 12, and then 1.7 mg subcutaneously once weekly for weeks 13 through 16. From week 17 and onward, a maintenance dose of 2.4 mg (recommended) or 1.7 mg subcutaneously once weekly. Consider delaying dose escalation for 4 weeks if a dose increase is not tolerated. Assess treatment response and tolerability when selecting the maintenance dose.[66713]

    Children and Adolescents 12 to 17 years

    0.25 mg subcutaneously once weekly for weeks 1 through 4, then 0.5 mg subcutaneously once weekly for weeks 5 through 8, then 1 mg subcutaneously once weekly for weeks 9 through 12, then 1.7 mg subcutaneously once weekly for weeks 13 through 16, and then 2.4 mg subcutaneously once weekly. Consider delaying dose escalation for 4 weeks if a dose increase is not tolerated. May decrease dose to 1.7 mg subcutaneously once weekly if the 2.4 mg dose is not tolerated. Discontinue use if the 1.7 mg dose is not tolerated.[66713]

    Therapeutic Drug Monitoring

    • Individualize glycemic goals based on a risk-benefit assessment.
    • Use higher goals in patients with persistent hypoglycemia.
    • Monitor post-prandial glucose concentrations if there is any inconsistency between pre-prandial glucose and A1C concentrations and to help assess basal-bolus regimens.[64926]

     

    Blood glucose goals for adults with type 1 or type 2 diabetes [64926]:

    • Pre-prandial = 80 to 130 mg/dL
    • Peak post-prandial = less than 180 mg/dL

     

    A1C goals for adults with type 1 or type 2 diabetes [64926]:

    • Assess A1C at least 2 times a year in patients who are meeting treatment goals (and who have stable glycemic control). Perform A1C test quarterly in patients whose therapy has changed or who are not meeting glycemic goals.
    • In general, an A1C target is less than 7% in nonpregnant adults.[50321][64926]
      • A more stringent goal of less than 6.5% may be appropriate for selected individual patients if this can be achieved without significant hypoglycemia or other adverse effects.[60608]
      • Less stringent goals (e.g., A1C less than 8%) may be appropriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced microvascular/macrovascular complications, or extensive comorbid conditions.[64926]

    Maximum Dosage Limits

    • Adults

      2 mg/week subcutaneously for the treatment of type 2 diabetes mellitus; 2.4 mg/week subcutaneously for the treatment of obesity; 14 mg/day PO for the treatment of type 2 diabetes mellitus.

    • Geriatric

      2 mg/week subcutaneously for the treatment of type 2 diabetes mellitus; 2.4 mg/week subcutaneously for the treatment of obesity; 14 mg/day PO for the treatment of type 2 diabetes mellitus.

    • Adolescents

      2.4 mg/week subcutaneously for the treatment of obesity; safety and efficacy have not been established for the treatment of type 2 diabetes mellitus.

    • Children

      12 years: 2.4 mg/week subcutaneously for the treatment of obesity; safety and efficacy have not been established for the treatment of type 2 diabetes mellitus.

      1 to 11 years: Safety and efficacy have not been established.

    • Infants

      Safety and efficacy have not been established.

    Patients with Hepatic Impairment Dosing

    No dosage adjustments are needed.[62656][64637][66713]

    Patients with Renal Impairment Dosing

    No dosage adjustments are needed.[62656][64637][66713]

    † Off-label indication
    Revision Date: 03/28/2024, 01:48:00 AM

    References

    50321 - Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2018;41:2669-2701.60608 - Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus Statement by The American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm 2019 Executive Summary. Endocrine Pract 2019;25:69-100.62656 - Ozempic (semaglutide solution for injection) package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2023 Sept.64637 - Rybelsus (semaglutide tablets) package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2024 Jan.64926 - American Diabetes Association. Standards of Medical Care in Diabetes - 2024. Diabetes Care. 2024; 47(Suppl 1):S1-S321. Available at: https://diabetesjournals.org/care/issue/47/Supplement_166713 - Wegovy (semaglutide) injection package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2024 Mar.

    How Supplied

    Semaglutide Oral tablet

    RYBELSUS 3mg Tablet (00169-4303) (Novo Nordisk Inc.) nullRYBELSUS 3mg Tablet package photo

    Semaglutide Oral tablet

    RYBELSUS 7mg Tablet (00169-4307) (Novo Nordisk Inc.) nullRYBELSUS 7mg Tablet package photo

    Semaglutide Oral tablet

    RYBELSUS 14mg Tablet (00169-4314) (Novo Nordisk Inc.) nullRYBELSUS 14mg Tablet package photo

    Semaglutide Solution for injection

    OZEMPIC 0.25mg or 0.5mg Dose 2mg/3mL Pen Injector (00169-4181) (Novo Nordisk Inc.) nullOZEMPIC 0.25mg or 0.5mg Dose 2mg/3mL Pen Injector package photo

    Semaglutide Solution for injection

    OZEMPIC 0.25mg, 0.5mg Dose 1.5mL 1.34mg/mL Pen Injector (00169-4132) (Novo Nordisk Inc.) (off market)OZEMPIC 0.25mg, 0.5mg Dose 1.5mL 1.34mg/mL Pen Injector package photo

    Semaglutide Solution for injection

    OZEMPIC 1mg Dose 1.5mL 1.34mg/mL Pen Injector (00169-4136) (Novo Nordisk Inc.) (off market)OZEMPIC 1mg Dose 1.5mL 1.34mg/mL Pen Injector package photo

    Semaglutide Solution for injection

    OZEMPIC 1mg Dose 2mg/1.5mL Pen Injector (00169-4136) (Novo Nordisk Inc.) null

    Semaglutide Solution for injection

    OZEMPIC 3mL 1.34mg/mL Pen Injector (50090-5949) (A-S Medication Solutions LLC) null

    Semaglutide Solution for injection

    OZEMPIC 3mL 1.34mg/mL Pen Injector (00169-4130) (Novo Nordisk Inc.) nullOZEMPIC 3mL 1.34mg/mL Pen Injector package photo

    Semaglutide Solution for injection

    OZEMPIC 3mL 2.68mg/mL Pen Injector (50090-6051) (A-S Medication Solutions LLC) null

    Semaglutide Solution for injection

    OZEMPIC 3mL 2.68mg/mL Pen Injector (00169-4772) (Novo Nordisk Inc.) nullOZEMPIC 3mL 2.68mg/mL Pen Injector package photo

    Semaglutide Solution for injection [Weight Management]

    Wegovy 0.25mg/dose Pre-Filled Pen Solution for Injection (50090-5824) (A-S Medication Solutions LLC) null

    Semaglutide Solution for injection [Weight Management]

    Wegovy 0.25mg/dose Pre-Filled Pen Solution for Injection (00169-4525) (Novo Nordisk Inc.) nullWegovy 0.25mg/dose Pre-Filled Pen Solution for Injection package photo

    Semaglutide Solution for injection [Weight Management]

    Wegovy 0.5mg/dose Pre-Filled Pen Solution for Injection (00169-4505) (Novo Nordisk Inc.) nullWegovy 0.5mg/dose Pre-Filled Pen Solution for Injection package photo

    Semaglutide Solution for injection [Weight Management]

    Wegovy 1.7mg/dose Pre-Filled Pen Solution for Injection (00169-4517) (Novo Nordisk Inc.) nullWegovy 1.7mg/dose Pre-Filled Pen Solution for Injection package photo

    Semaglutide Solution for injection [Weight Management]

    Wegovy 1mg/dose Pre-Filled Pen Solution for Injection (00169-4501) (Novo Nordisk Inc.) null

    Semaglutide Solution for injection [Weight Management]

    Wegovy 2.4mg/dose Pre-Filled Pen Solution for Injection (00169-4524) (Novo Nordisk Inc.) nullWegovy 2.4mg/dose Pre-Filled Pen Solution for Injection package photo

    Description/Classification

    Description

    Semaglutide is a synthetic glucagon-like peptide-1 receptor agonist (GLP-1 RA) that belongs to a class of antidiabetic agents called incretin mimetics. Incretins are endogenous compounds, including glucagon-like peptide-1 (GLP-1), that improve glycemic control once released into the circulation via the gut. Semaglutide subcutaneous injection (Ozempic) and oral tablets (Rybelsus) are used as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM).[62656][64637] Semaglutide subcutaneous injection (Ozempic) is also used to reduce the risk of non-fatal cardiovascular (CV) events and CV mortality in T2DM patients with CV disease.[62656][64937] Semaglutide oral tablets demonstrated CV safety by meeting the primary endpoint of non-inferiority for the composite major cardiovascular events (MACE) endpoint; the proportion of patients who experienced at least one MACE was 3.8% with semaglutide oral tablets and 4.8% with placebo.[64938] However, semaglutide oral tablets are not approved for the reduction of CV events.[64637] As with other agents in this class, semaglutide has a boxed warning regarding rodent thyroid C-cell tumor findings and the uncertain relevance to humans.[62656][64637] First-line T2DM therapy depends on comorbidities, patient-centered treatment factors, and management needs. In adults with T2DM and established atherosclerotic cardiovascular disease (ASCVD) or indicators of high ASCVD risk, a GLP-1 RA with proven CV benefit (e.g., liraglutide, semaglutide, or dulaglutide) should be initiated as a first-line therapy independent of A1C goal or other antihyperglycemic treatments, including metformin. Alternatively, a sodium-glucose co-transporter 2 inhibitor (SGLT2 inhibitor) with proven CV benefit (e.g., canagliflozin, empagliflozin), may be used to reduce the risk of MACE or CV death in persons with T2DM and established ASCVD. GLP-1 RAs improve CV outcomes, as well as secondary outcomes such as progression of renal disease, in patients with established CV disease or chronic kidney disease (CKD); these factors make GLP-1 RA therapy an alternative initial treatment option, with or without metformin based on glycemic needs, in T2DM patients with indicators of high-risk or established heart failure (HF) or CKD who cannot tolerate an SGLT2 inhibitor. In patients with T2DM who do not have ASCVD/indicators of high-risk, HF, or CKD and who need to minimize hypoglycemia and/or promote weight loss, GLP-1 RAs, including dual glucose-dependent insulinotropic polypeptide (GIP)/ GLP-1 agonists are generally recommended as a second-line option as add-on to metformin therapy. GLP-1 RAs and dual GIP/ GLP-1 agonists have high glucose-lowering efficacy, with dulaglutide (high dose), semaglutide, and tirzepatide having the greatest efficacy, followed by exenatide, liraglutide, and lixisenatide. Semaglutide and tirzepatide produce the most weight loss, followed by dulaglutide and liraglutide, and then exenatide and lixisenatide.[50321][64926][60608] A separate product, semaglutide subcutaneous injection (Wegovy), is indicated as an adjunct to lifestyle modifications for weight loss and chronic weight management for obese (BMI 30 kg/m2 or greater) or overweight adults (BMI 27 kg/m2 or greater) with at least 1 weight-related comorbid condition (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia) and for pediatric patients aged 12 years and older with an initial BMI at the 95th percentile or greater. Semaglutide subcutaneous injection (Wegovy) is also indicated to reduce the risk of MACE in adults with established cardiovascular disease and obesity or who are overweight. Four clinical trials for weight management were conducted pre-approval in adults. Depending on the clinical trial, more treated participants lost 5% up to 15% of their initial body weight vs. those taking placebo. In a clinical trial in pediatric patients 12 years and older, patients experienced a 14.7% decrease in body weight from baseline while placebo-treated patients experienced a 2.7% increase in bodyweight. In a cardiovascular outcomes trial with semaglutide injection for weight management in adults, semaglutide reduced the risk for first occurrence of MACE (hazard ratio 0.8 (95% CI 0.72 to 0.9)).[66713] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, weight loss medications should be offered as chronic treatment along with lifestyle modifications to patients with obesity when the potential benefits outweigh the risks. Short-term pharmacotherapy has not been shown to produce longer-term health benefits and cannot be generally recommended. A generalized hierarchy for medication preferences that would apply to all overweight patients cannot currently be scientifically justified. Individualized weight loss pharmacotherapy is recommended, based upon factors such as the specific characteristics of each weight loss medication, the presence of weight-related complications, and the medical history of the patient.[62881]

     

    NOTE: In December 2023, the FDA warned consumers not to use counterfeit semaglutide (Ozempic or Wegovy). Wholesalers, retail pharmacies, health care practitioners and patients are advised to check the products they have received and not distribute, use, or sell products labeled with lot number NAR0074 and serial number 430834149057. The FDA and Novo Nordisk are testing the seized products and do not yet have information about the drugs' identity, quality, or safety. Analysis found the needles from the samples are counterfeit and therefore, the sterility of the needles cannot be confirmed, which presents an increased risk of infection. Other confirmed counterfeit components within the seized products are the pen label, accompanying health care professional and patient information, and carton. The FDA is aware of 5 adverse events from this lot, none of which are serious and are consistent with known common adverse reactions to authentic semaglutide. FDA recommends retail pharmacies only purchase authentic products through authorized distributors and review the photographs and information to confirm the legitimacy of their shipments. Patients should only obtain semaglutide products with a valid prescription through state-licensed pharmacies and check the product before using for any signs of counterfeiting. Health care professionals and consumers should report adverse events related to the use of this product to FDA's MedWatch Safety Information and Adverse Event Reporting Program. Retailers and patients may also contact Novo Nordisk customer care at 1-800-727-6500 with questions or concerns.[70063]

    Classifications

    • Alimentary Tract and Metabolism
      • Agents for Obesity
        • Glucagon-like Peptide-1 (GLP-1) Receptor Agonists for Obesity
      • Antidiabetic Agents
        • Blood Glucose Lowering Agents, excluding Insulins
          • Incretin mimetics Antidiabetics
            • Glucagon-like Peptide-1 (GLP-1) Receptor Agonists
    Revision Date: 03/28/2024, 01:48:00 AM

    References

    50321 - Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2018;41:2669-2701.60608 - Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus Statement by The American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm 2019 Executive Summary. Endocrine Pract 2019;25:69-100.62656 - Ozempic (semaglutide solution for injection) package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2023 Sept.62881 - Garvey WT, Mechanick JI, Brett EM, et al; Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines. American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract. 2016 Jul;22 Suppl 3:1-203. Epub 2016 May 24.64637 - Rybelsus (semaglutide tablets) package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2024 Jan.64926 - American Diabetes Association. Standards of Medical Care in Diabetes - 2024. Diabetes Care. 2024; 47(Suppl 1):S1-S321. Available at: https://diabetesjournals.org/care/issue/47/Supplement_164937 - Marso SP, Bain SC, Consoli A, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med 2016;375:1834-1844.64938 - Husain M, Birkenfeld AL, Donsmark M, et al. Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med 2019;381:841-851.66713 - Wegovy (semaglutide) injection package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2024 Mar.70063 - U.S. Food and Drug Administration. Ozempic (semaglutide): Drug Safety Communication - FDA warns consumers not to use counterfeit Ozempic (semaglutide) found in U.S. drug supply chain. December 21, 2020. Available at: https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-consumers-not-use-counterfeit-ozempic-semaglutide-found-us-drug-supply-chain. Accessed December 29th, 2023.

    Administration Information

    General Administration Information

    For storage information, see the specific product information within the How Supplied section.

    Route-Specific Administration

    Oral Administration

    Oral Solid Formulations

    • Administer the tablets at least 30 minutes before the first food, beverage, or other oral medications of the day with no more than 4 ounces of plain water. Waiting less than 30 minutes, or taking semaglutide with food, beverages (other than plain water) or other oral medications will reduce efficacy of semaglutide by decreasing its absorption. Waiting more than 30 minutes to eat may increase the absorption of semaglutide.
    • The patient should swallow tablets whole. Do not split, crush, or chew tablets.
    • Missed dose: If a dose is missed, the missed dose should be skipped, and the next dose should be taken the following day.[64637]

    Injectable Administration

    • Administer by subcutaneous injection only. Do not administer by intravenous or intramuscular injection.
    • Visually inspect for particulate matter and discoloration prior to administration whenever solution and container permit.
    • Injection pens should never be shared among patients. Even if the disposable needle is changed, sharing may result in transmission of hepatitis viruses, HIV, or other blood-borne pathogens. Do not share pens among multiple patients in an inpatient setting; reserve the use of any pen to 1 patient only.[54923][58866][62656][66713]

    Subcutaneous Administration

    Ozempic Pen

    General information

    • Ozempic Pen is available as a pre-filled "dial a dose" pen (0.25, 0.5, 1, and 2 mg). The pen should be used with NovoFine Plus or Novofine disposable needles up to a length of 8 mm. The pen comes with NovoFine Plus 32-gauge 4 mm disposable needles.
    • When used concomitantly with insulin therapy, administer as separate injections. Never mix them together. The two injections may be injected in the same body region, but the injections should not be adjacent to each other.
    • Instruct patients/caregivers on proper injection technique. Adequate oral and written instructions on the use of the pen should be supplied before a patient or caregiver administers a dose. Patients/caregivers should review the "Instructions for Use" in their pen package. People who are blind or have vision problems should not use the pen without help from a person trained to use the pen.
    • Administer every 7 days (once weekly) on the same day each week; the dose can be administered at any time of day, with or without meals.
    • Missed dose: If a dose is missed, give as soon as possible within 5 days after the missed dose. If more than 5 days have passed, skip the missed dose and administer on the next scheduled day. The day of weekly administration can be changed if needed, as long as the time between 2 doses is at least 2 days (more than 48 hours).[62656]

    Subcutaneous Pen Administration (Ozempic Pen)

    • Wash and dry hands before use.
    • Each semaglutide pen must be primed prior to the first use. See the pen user manual for priming directions.
    • Always attach a new needle right before each injection. Pull the pen cap off, but do not throw it away. Push the needle straight onto the pen. Turn until it is on tight. Pull off the inner needle cap and throw it away.
    • Turn the dose selector on the pen until the dose counter shows the dose. Double-check the dosage selected prior to administration.
    • Inject subcutaneously into the thigh, abdomen, or upper arm.
    • Press down in the center of the dose button to inject until the "0" lines up with the pointer. Inject over 6 seconds to ensure the full dose is injected. The patient may hear or feel a 'click'. Keep thumb on the injection button until the needle is removed from the skin. Remove the needle from the skin.
    • Remove and dispose of the used needle in an appropriate sharps container after each injection.
    • Place the pen cap back on the pen.
    • Rotate administration sites with each injection to prevent lipodystrophy.
    • Storage of opened pens: Do not store the "in-use" pen with the needle on; this will reduce the potential for contamination, infection, and leakage and will help ensure dosing accuracy. The open pen can be stored for 56 days below 86 degrees F (30 degrees C) or in a refrigerator at 36 to 46 degrees F (2 to 8 degrees C). Do not freeze. Throw away the pen after 56 days, even if it still has medication left in it.[62656]

     

    Wegovy Pen

    General information

    • Wegovy Pen is available in 5 pre-filled, disposable, single-dose pens (0.25, 0.5, 1, 1.7, and 2.4 mg). Ensure the correct dose of the pen is chosen for the dose to be administered.
    • Administer once every 7 days (once weekly) on the same day each week; the dose can be administered at any time of day, with or without meals.
    • Administer in combination with a reduced-calorie diet and increased physical activity.
    • Instruct patients/caregivers on proper injection technique. Adequate oral and written instructions on the use of the pen should be supplied before a patient or caregiver administers a dose. Patients/caregivers should review the "Instructions for Use" in their pen package. People who are blind or have vision problems should not use the pen without help from a person trained to use the pen.
    • Missed dose: If 1 dose is missed and the next scheduled dose is more than 2 days away (48 hours), administer dose as soon as possible. If 1 dose is missed and the next scheduled dose is less than 2 days away (48 hours), do not administer the dose. Resume dosing on the regularly scheduled day of the week. If more than 2 consecutive doses are missed, resume dosing as scheduled. Alternatively, if needed, restart the initial titration schedule, which may reduce the occurrence of gastrointestinal symptoms associated with reinitiating treatment.[66713]

    Subcutaneous Pen Administration (Wegovy Pen)

    • Wash and dry hands before use.
    • The dose of semaglutide is already set on the Wegovy pen; each pen is for one-time use only.
    • The needle is covered by the needle cover and will not be seen. Do not remove the pen cap until ready to inject; do not touch or push the needle cover to avoid a needle stick injury.
    • Inject subcutaneously into the thigh, abdomen, or upper arm by pressing the needle cap firmly against the skin; this will begin the injection. Do not inject into an area where the skin is tender, bruised, red, or hard. Avoid injecting into areas with scars or stretch marks.
    • Do not remove the pen from the skin before the yellow bar in the pen window has stopped moving. The medication may appear on the skin or squirt from the needle and the full dose may not be received if the pen is removed too early or the pen is not pressed firmly against the skin for the entire injection. The needle cover will lock when it is removed from the skin. The injection cannot be stopped and restarted later.
    • If the yellow bar does not start moving or stops moving during the injection, advise the patient to contact their health care provider or Novo Nordisk at startWegovy.com or call Novo Nordisk Inc. at 1-833-934-6891.
    • Dispose of the used pen in an appropriate sharps container after each injection. Each Wegovy pen is for single-use only.
    • Rotate administration sites with each injection to prevent lipodystrophy.[66713]

    Clinical Pharmaceutics Information

    From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database

    Semaglutide

    pH Range
    pH approximately 7.4
    ReferencesOzempic (Semaglutide) injection package insert. Plainsboro, NJ. Novo Nordisk Inc. 2023; Sep
      Revision Date: 03/28/2024, 01:48:00 AMCopyright 2004-2024 by Lawrence A. Trissel. All Rights Reserved.

      References

      54923 - Institute for Safe Medication Practices. Ongoing concern about insulin pen reuse shows hospitals need to consider transitioning away from the pen. ISMP Medication Safety Alert. Retrieved from the World Wide Web June 4, 2013. http://www.ismp.org/newsletters/acutecare/showarticle.asp?id=41.58866 - Food and Drug Administration Drug Safety Communication: FDA requires label warnings to prohibit sharing of multi-dose diabetes pen devices among patients. Retrieved February 26, 2015. Available on the World Wide Web at: http://fda.gov/Drugs/DrugSafety/ucm43571.htm.62656 - Ozempic (semaglutide solution for injection) package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2023 Sept.64637 - Rybelsus (semaglutide tablets) package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2024 Jan.66713 - Wegovy (semaglutide) injection package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2024 Mar.

      Adverse Reactions

      Mild

      • abdominal pain
      • alopecia
      • anxiety
      • diarrhea
      • dizziness
      • dysesthesia
      • dysgeusia
      • dyspepsia
      • eructation
      • fatigue
      • flatulence
      • gastroesophageal reflux
      • headache
      • hiccups
      • infection
      • influenza
      • injection site reaction
      • nausea
      • paresthesias
      • pharyngitis
      • rash
      • sinusitis
      • syncope
      • urticaria
      • vomiting

      Moderate

      • antibody formation
      • cholelithiasis
      • constipation
      • dehydration
      • depression
      • elevated hepatic enzymes
      • gastritis
      • hemorrhoids
      • hyperamylasemia
      • hyperbilirubinemia
      • hyperesthesia
      • hypoglycemia
      • hypotension
      • nephrolithiasis
      • orthostatic hypotension
      • sinus tachycardia

      Severe

      • anaphylactoid reactions
      • angioedema
      • appendicitis
      • bone fractures
      • cholecystitis
      • ileus
      • new primary malignancy
      • pancreatitis
      • renal failure
      • retinopathy
      • suicidal ideation

      In monotherapy trials with semaglutide injection for type 2 diabetes mellitus (T2DM), severe hypoglycemia (requiring the assistance of another person) was not reported in either the treatment group or the placebo group. Documented symptomatic hypoglycemia (glucose of 70 mg/dL or less) was reported in 1.6% to 3.8% of patients receiving semaglutide injection vs. 0% of patients receiving placebo. Severe or blood glucose confirmed symptomatic hypoglycemia (glucose of 56 mg/dL or less) was not reported in any of the patients receiving semaglutide monotherapy compared to 1.6% of patients receiving placebo. In trials where semaglutide was added on to basal insulin with or without metformin, severe hypoglycemia (requiring the assistance of another person) was reported in 1.5% of semaglutide-treated patients. Documented symptomatic hypoglycemia (glucose of 70 mg/dL or less) was reported in 16.7% to 29.8% of patients receiving semaglutide, and severe or blood glucose confirmed symptomatic hypoglycemia (glucose of 56 mg/dL or less) was reported in 8.3% to 10.7% of patients receiving semaglutide. Hypoglycemia was more frequent when semaglutide was used in combination with a sulfonylurea; severe hypoglycemia occurred in 0.8% and 1.2% of patients when semaglutide 0.5 mg and 1 mg, respectively, was given with a sulfonylurea. In addition, documented symptomatic hypoglycemia occurred in 17.3% and 24.4% of patients and severe or blood glucose confirmed symptomatic hypoglycemia (glucose of 56 mg/dL or less) occurred in 6.5% and 10.4% of patients when semaglutide 0.5 mg and 1 mg, respectively, was given with a sulfonylurea.[62656] In monotherapy trials with semaglutide oral tablets for T2DM, severe hypoglycemia (requiring the assistance of another person) was reported in 1% of patients receiving the 7 mg tablets and 0% of patients receiving the 14 mg tablets or placebo. A blood glucose level of 54 mg/dL or less occurred in 1% of patients receiving placebo and 0% of the semaglutide oral treatment groups. Severe hypoglycemia was not reported in any patients enrolled in trials where semaglutide tablets were added on to metformin and/or sulfonylurea, basal insulin alone, or metformin in combination with basal insulin in patients with moderate renal impairment. In contrast, blood glucose level of 54 mg/dL or less occurred in 6% of patients receiving the 14 mg tablets and 3% of patients receiving placebo. In trials when semaglutide was added on to insulin with or without metformin, severe hypoglycemia was reported in 1% of patients receiving the 14 mg tablets, 1% of patients receiving placebo, and 0% of the patients receiving the 7 mg tablets. A blood glucose level of 54 mg/dL or less was reported in 26% of patients receiving the 7 mg tablets, 30% of patients receiving the 14 mg tablets, and 32% with placebo.[64637] In a trial of patients with T2DM and a BMI of 27 kg/m2 or greater being treated with semaglutide injection for weight loss, clinically significant hypoglycemia (plasma glucose less than 54 mg/dL) was reported in 6.2% of semaglutide-treated patients versus 2.5% of placebo-treated patients. A higher rate of clinically significant hypoglycemic episodes was reported with the semaglutide 2.4 mg/week dose versus the 1 mg/week dose (10.7 vs. 7.2 episodes per 100 patient-years of exposure, respectively); the rate in the placebo-treated group was 3.2 episodes per 100 patient years of exposure. In addition, one episode of severe hypoglycemia requiring intravenous glucose was reported in a semaglutide-treated patient. The risk of hypoglycemia was increased when semaglutide was used with a sulfonylurea. In a cardiovascular outcomes trial in adults without T2DM, 3 episodes of serious hypoglycemia were reported in semaglutide-treated patients compared to 1 episode in placebo-treated patients. Patients with a history of bariatric surgery, a risk factor for hypoglycemia, had more events of serious hypoglycemia while taking semaglutide (2.3%) compared to placebo (0%).[66713]

      As with other GLP-1 analogs, gastrointestinal (GI) events are the most commonly reported adverse effects with semaglutide. More patients receiving semaglutide discontinued treatment due to GI adverse reactions than patients receiving placebo during all clinical trials. The following adverse effects were reported in patients receiving semaglutide injection or oral tablets across all clinical trials and at incidences higher than with placebo: nausea (11% to 44%), vomiting (5% to 36%), diarrhea (8.5% to 30%), abdominal pain (5.7% to 20%), abdominal distention (2% to 7%), constipation (3.1% to 24%), dyspepsia (0.6% to 9%), decreased appetite (6% to 9%), eructation (0.6% to 7%), flatulence (0.4% to 6%), gastroesophageal reflux disease (1.5% to 5%), gastroenteritis (4% to 7%), and gastritis (0.4% to 4%). The majority of reports of nausea, vomiting, and/or diarrhea occurred during dose escalation. Appendicitis was reported in 10 (0.5%) semaglutide-treated patients vs. 2 (0.2%) placebo-treated patients during clinical trials of semaglutide injection used for weight management. In the trial with semaglutide 1 mg and 2 mg injection for type 2 diabetes mellitus, GI events occurred more frequently among patients receiving semaglutide 2 mg injection (34%) compared to semaglutide 1 mg injection (30.8%). Ileus has been reported during postmarketing experience with both oral and subcutaneous semaglutide. Additionally, hemorrhoids and hiccups have also been reported in clinical trials with semaglutide injection for weight management.[62656] [64637] [66713]

      Acute gallbladder disease events, such as cholecystitis or cholelithiasis, have been reported in clinical studies with semaglutide. In clinical trials of semaglutide injection for type 2 diabetes mellitus (T2DM), cholelithiasis was reported in 1.5% and 0.4% of patients treated with semaglutide 0.5 mg and 1 mg subcutaneous injection, respectively. Cholelithiasis was not reported in placebo-treated patients.[62656] In clinical trials of oral semaglutide for T2DM, cholelithiasis was reported in 1% of patients treated with semaglutide 7 mg PO. Cholelithiasis was not reported in patients receiving the 14 mg PO or placebo-treated patients.[64637] In clinical trials of semaglutide injection for weight management in adults, cholelithiasis was reported in 1.6% of semaglutide-treated patients compared with 0.7% of placebo-treated patients. Cholecystitis was reported in 0.6% of semaglutide-treated patients (vs. 0.2%, placebo). In clinical trials of semaglutide injection for weight management in pediatric patients, cholelithiasis (3.8%) and cholecystitis (0.8%) were reported in semaglutide-treated patients compared to 0% placebo-treated patients. Substantial or rapid weight loss can increase the risk of cholelithiasis; however, the incidence of acute gallbladder disease was greater in semaglutide-treated patients than in placebo-treated patients, even after accounting for the degree of weight loss.[66713] Cholecystectomy has been reported during postmarketing use.[62656] During clinical trials in pediatric patients 12 years and older, elevated hepatic enzymes (increased alanine aminotransferase [ALT]) greater than or equal to 5 times the upper limit of normal were observed in 3% of semaglutide-treated patients compared to 0% of placebo-treated patients. In some patients, increases in ALT and AST were associated with other confounding factors (i.e., gallstones). Additionally, in a cardiovascular outcomes trial in adults without T2DM, hyperbilirubinemia (total bilirubin of 3 or more times the upper limit of normal) was reported in 0.3% of semaglutide-treated patients compared to 0.2% of placebo-treated patients.[66713]

      In placebo-controlled trials of semaglutide injection for type 2 diabetes mellitus, fatigue, dysgeusia, and dizziness were reported in greater than 0.4% of semaglutide-treated patients.[62656] Dysgeusia (1.7%) was also reported in clinical trials with semaglutide injection for weight management.[66713] In placebo-controlled trials of semaglutide injection for weight management, headache (14% to 17%), fatigue (11%), dizziness (8%), and anxiety (4%) were reported in treated patients.[66713] Suicidal behavior and suicidal ideation have been reported in clinical trials with other incretin mimetics indicated for weight management. Monitor patients for the emergence or worsening of depression, suicidal thoughts or behavior, and any unusual changes in moods or behaviors. Discontinue semaglutide in patients who develop suicidal thoughts or behaviors.[66713] In January 2024, the FDA announced that they have not found evidence that use of GLP-1 RAs for type 2 diabetes or weight management causes suicidal thoughts or actions. During their preliminary evaluation, they conducted detailed reviews of reports of suicidal thoughts or actions received in the FDA Adverse Event Reporting System (FAERS) and reviews of clinical trials, including large outcome studies and observational studies. However, because of the small number of suicidal thoughts or actions observed in both people using GLP-1 RAs and in the comparative control groups, they cannot definitively rule out that a small risk may exist; therefore, FDA is continuing to look into this issue. Further evaluations include a meta-analysis of clinical trials across all GLP-1 RA products and an analysis of postmarketing data in the Sentinel System; final conclusions and recommendations will be communicated once more information is known.[70130]

      In placebo-controlled trials for type 2 diabetes mellitus, an injection site reaction (e.g., injection-site discomfort, erythema) was reported in 0.2% of patients receiving semaglutide. In clinical trials, 1.4% of patients treated with semaglutide injection for weight management experienced injection site reactions (including injection site pruritus, erythema, inflammation, induration, and irritation) vs. 1% with placebo.[62656] [66713]

      Antibody formation against semaglutide has been reported. In clinical trials with semaglutide injection for type 2 diabetes mellitus (T2DM), 32 (1%) patients receiving semaglutide tested positive for anti-semaglutide antibodies. Of these 32 semaglutide-treated patients that developed anti-semaglutide antibodies, 19 patients (0.6% of the overall population) developed antibodies cross-reacting with native GLP-1.[62656] In clinical trials with semaglutide oral tablets for T2DM, 14 (0.5%) patients developed anti-semaglutide antibodies. Of the 14 semaglutide-treated patients that developed anti-semaglutide antibodies, 7 patients (0.2% of the overall population) developed antibodies cross-reacting with native GLP-1.[64637] In clinical trials with semaglutide injection for weight management, 50 (3%) patients receiving semaglutide tested positive for anti-semaglutide antibodies. Of these 50 semaglutide-treated patients that developed anti-semaglutide antibodies, 28 patients (2% of the overall population) developed antibodies cross-reacting with native GLP-1.[66713] The in vitro neutralizing activity of the antibodies is uncertain at this time. The incidence of antibodies to semaglutide cannot be directly compared with the incidence of antibodies of other products.[62656] [64637] [66713]

      There have been postmarketing reports of acute renal failure (unspecified) and worsening of chronic renal failure, which occasionally required hemodialysis, in patients treated with GLP-1 receptor agonists. Some of these events were reported in patients without known underlying renal disease. A majority of reported events occurred in patients who had experienced gastrointestinal reactions such as nausea, vomiting, diarrhea, or dehydration. In clinical trials of semaglutide injection for weight management, acute kidney injury occurred in 7 patients (0.4 cases per 100 patient-years) receiving semaglutide vs. 4 patients (0.2 cases per 100 patient-years) receiving placebo. The risk of renal adverse reactions was increased in patients with a history of renal impairment (the weight management trials included 65 patients with a history of moderate or severe renal impairment at baseline), and occurred more frequently during dose titration. Monitor renal function when initiating or escalating doses of semaglutide in patients reporting severe adverse GI reactions.[62656] [64637] [66713] In a cardiovascular outcomes trial involving adults without type 2 diabetes mellitus, nephrolithiasis (urolithiasis) was reported in 1.2% of semaglutide-treated patients vs. 0.8% of placebo-treated patients, including serious reactions that were reported more frequently in patients receiving semaglutide (0.6%) vs. placebo (0.4%).[66713]

      In clinical trials of semaglutide for type 2 diabetes mellitus (T2DM), patients exposed to semaglutide subcutaneous injection reported increases in amylase (hyperamylasemia) and lipase, and had a mean increase from baseline in amylase of 13% and lipase of 22%. These changes were not observed in placebo-treated patients.[62656] In trials with semaglutide oral tablets, patients exposed to semaglutide 7 mg and 14 mg oral tablets had a mean increase from baseline in amylase of 10% and 13%, respectively, and lipase of 30% and 34%, respectively. These changes were not observed in placebo-treated patients.[64637] In clinical trials of semaglutide injection for weight management, patients treated with semaglutide had a mean increase from baseline in amylase of 15% to 16% and lipase of 39%. These changes were not observed in the placebo group.[66713] There have been reports of acute pancreatitis in patients taking semaglutide during premarketing trials. In glycemic control trials with semaglutide injection, acute pancreatitis was reported in 7 semaglutide-treated patients (0.3 cases per 100 patient-years) versus 3 in comparator-treated patients (0.2 cases per 100 patient-years). One case of chronic pancreatitis was confirmed in a semaglutide-treated patient. In a 2-year trial, acute pancreatitis was reported in 8 semaglutide-treated patients (0.27 cases per 100 patient-years) and 10 placebo-treated patients (0.33 cases per 100 patient-years), both on a background of standard of care.[62656] In trials of patients receiving oral semaglutide, pancreatitis was reported as a serious adverse event in 6 patients (0.1 events per 100 patient-years) receiving semaglutide versus 1 in comparator-treated patients (less than 0.1 events per 100 patient-years).[64637] In clinical trials of semaglutide injection for weight management, acute pancreatitis was confirmed by adjudication in 4 semaglutide-treated patients (0.2 cases per 100 patient-years) versus 1 in placebo-treated patients (less than 0.1 cases per 100 patient-years). One additional case of acute pancreatitis was confirmed in a patient treated with semaglutide in another clinical trial.[66713] The FDA and the EMA have stated that after review of published and unpublished reports, the current data do not support an increased risk of pancreatitis and pancreatic cancer in patients receiving incretin mimetics. The agencies have not reached any new conclusions about safety risks of the incretin mimetics, although they have expressed that the totality of the data that have been reviewed provides reassurance. Continue to consider precautions related to pancreatic risk until more data are available.[53573] [56778] After treatment initiation and dose increases, patients should be observed carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back and which may or may not be accompanied by vomiting). Semaglutide for T2DM has not been studied in patients with a history of pancreatitis and there is limited data from clinical trials with semaglutide injection for weight management. It is not known whether these patients are at an increased risk for developing pancreatitis.[62656] [64637] [66713]

      During a clinical trial in pediatric patients 12 years and older receiving semaglutide for weight management, rash (3%) and urticaria (3%) were reported. Hypersensitivity reactions, including anaphylaxis, anaphylactoid reactions, angioedema, rash, and urticaria, have been reported postmarketing with use of semaglutide.[62656] [64637] [66713]

      Sinus tachycardia was observed during clinical studies of semaglutide injection for weight management; mean increases in resting heart rate of 1 to 4 beats per minute (bpm) were seen with routine clinical monitoring in semaglutide-treated patients vs. placebo. More patients treated with semaglutide than with placebo had maximum changes from baseline at any visit of 10 to 19 bpm (41% vs. 34%, respectively) and 20 bpm or more (26% vs. 16%, respectively). In a clinical trial of pediatric patients aged 12 years and older, more patients treated with semaglutide compared to placebo had maximum changes in heart rate of 20 bpm or more (54% versus 39%). In placebo-controlled trials for type 2 diabetes mellitus (T2DM), semaglutide injection 0.5 and 1 mg resulted in a mean increase in heart rate of 2 to 3 bpm. There was a mean decrease in heart rate of 0.3 bpm in placebo-treated patients. In placebo-controlled trials of oral semaglutide for T2DM, semaglutide 7 and 14 mg resulted in a mean increase in heart rate of 2 to 3 bpm. There was no change in heart rate in placebo-treated patients. Heart rate should be monitored at regular intervals consistent with usual clinical practice in patients taking semaglutide and patients should inform health care providers of palpitations or feelings of a racing heartbeat while at rest during semaglutide treatment. For patients who experience a sustained increase in resting heart rate while taking semaglutide, the drug should be discontinued.[62656] [64637] [66713] Adverse reactions related to hypotension (hypotension, orthostatic hypotension, and decreased blood pressure) were reported in 1.3% to 2.3% of semaglutide-treated patients versus 0% to 0.4% of placebo-treated patients during clinical trials of semaglutide injection for weight management. Syncope was reported in 0.8% and 0.2% of patients, respectively. Some reactions were related to gastrointestinal adverse reactions and volume loss associated with semaglutide. In adult patients, hypotension and orthostatic hypotension were more frequently seen in patients on concomitant antihypertensive therapy.[66713]

      Hair loss (alopecia) was reported in 3% to 4% of patients receiving semaglutide injection for weight management during clinical trials vs. 0% to 1% of patients receiving placebo.[66713]

      Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. In a 2-year trial involving patients with type 2 diabetes mellitus (T2DM) and high cardiovascular risk, more events of diabetic retinopathy complications occurred in the patients treated with semaglutide injection (3%) compared to placebo (1.8%). The absolute risk increase for diabetic retinopathy complications was greater among patients with a history of diabetic retinopathy at baseline (semaglutide 8.2%, placebo 5.2%) than among patients without a known history of diabetic retinopathy (semaglutide 0.7%, placebo 0.4%).[62656] In a pooled analysis of glycemic control trials with oral semaglutide for T2DM, diabetic retinopathy complications occurred in 4.2% of patients receiving semaglutide vs. 3.8% with comparator.[64637] In a trial of patients with T2DM and BMI 27 kg/m2 or more receiving semaglutide injection for weight management, retinal disorders were reported by 6.9% of patients treated with semaglutide 2.4 mg/week, 6.2% of patients treated with semaglutide 1 mg/week, and 4.2% of patients treated with placebo. The majority of events were reported as diabetic retinopathy (4%, 2.7%, and 2.7%, respectively) and non-proliferative retinopathy (0.7%, 0%, and 0%, respectively).[66713] The effect of long-term glycemic control with semaglutide on diabetic retinopathy complications has not been studied. Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy during treatment.[62656] [64637] [66713]

      Semaglutide may be associated with the development of a new primary malignancy. Nonclinical studies in rodents of clinically relevant doses of GLP-1 receptor agonists showed dose-related and treatment-duration-dependent increases in the incidence of thyroid C-cell tumors (adenomas and carcinomas). It is unknown whether GLP-1 receptor agonists are associated with thyroid C-cell tumors, including MTC in humans. Patients should be counseled on the risk and symptoms of thyroid tumors (e.g. symptoms may include a mass in the neck, dysphagia, dyspnea or persistent hoarseness). Although routine monitoring of serum calcitonin is of uncertain value in patients treated with semaglutide, if serum calcitonin is measured and found to be elevated, the patient should be referred to an endocrinologist for further evaluation.[62656] [64637] [66713]

      During a clinical trial in pediatric patients 12 years and older receiving semaglutide for weight management, naso-pharyngitis (12% vs. 10% placebo), sinusitis (4% vs. 2% placebo), urinary tract infection (4% vs. 2% placebo), and influenza (3% vs. 0% placebo) were reported. Ligament sprain was reported in 4% of pediatric patients 12 years and older receiving semaglutide for weight management compared to 2% of patients receiving placebo.[66713]

      In clinical trials with semaglutide injection for weight management, dysesthesia, which includes paresthesias, hyperesthesia, burning sensation/skin burning sensation, allodynia, skin pain, and sensitive skin, was reported in 2% of semaglutide-treated patients compared to 1% placebo.[66713]

      In a cardiovascular outcomes trial of adults without type 2 diabetes mellitus, bone fractures (e.g., hip and pelvis fractures) were reported more frequently in adult females and adults aged 75 years and older taking semaglutide (1% and 2.4%, respectively) compared to placebo (0.2% and 0.6%, respectively).[66713]

      Revision Date: 03/28/2024, 01:48:00 AM

      References

      53573 - Food and Drug Administration (US FDA) Drug Medwatch-FDA investigating reports of possible increased risk of pancreatitis and pre-cancerous findings of the pancreas from incretin mimetic drugs for type 2 diabetes. Retrieved Mar. 14, 2013. Available on the World Wide Web at http://www.fda.gov/Drugs/DrugSafety/ucm343187.htm.56778 - Egan AG, Blind E, Dunder K, , et al. Pancreatic safety of incretin-based drugs-FDA and EMA assessment. N Engl J Med 2014;370:794—7.62656 - Ozempic (semaglutide solution for injection) package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2023 Sept.64637 - Rybelsus (semaglutide tablets) package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2024 Jan.66713 - Wegovy (semaglutide) injection package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2024 Mar.70130 - US Food and Drug Administration (FDA). FDA Medwatch - Certain Type of Medicines Approved for Type 2 Diabetes and Obesity: Drug Safety Communication - Update on FDA’s Ongoing Evaluation of Reports of Suicidal Thoughts or Actions. Retrieved January 11, 2024. Available on the World Wide Web at: https://www.fda.gov/drugs/drug-safety-and-availability/update-fdas-ongoing-evaluation-reports-suicidal-thoughts-or-actions-patients-taking-certain-type.

      Contraindications/Precautions

      Absolute contraindications are italicized.

      • medullary thyroid carcinoma (MTC)
      • multiple endocrine neoplasia syndrome type 2 (MEN 2)
      • thyroid C-cell tumors
      • breast-feeding
      • cholelithiasis
      • depression
      • diabetic retinopathy
      • gallbladder disease
      • geriatric
      • history of angioedema
      • hypoglycemia
      • pancreatitis
      • pregnancy
      • renal failure
      • renal impairment
      • reproductive risk
      • schizophrenia
      • suicidal ideation
      • thyroid cancer
      • type 1 diabetes mellitus

      Semaglutide is contraindicated in patients with a history of angioedema, anaphylaxis, or other serious hypersensitivity reaction to semaglutide. There is a risk of serious hypersensitivity reactions with semaglutide. Serious hypersensitivity reactions have also been reported during postmarketing use with other GLP-1 receptor agonists. Use caution in patients with a history of anaphylaxis or angioedema to other GLP-1 receptor agonists because it is unknown whether such patients will be predisposed to serious reactions with semaglutide. If a serious hypersensitivity reaction is suspected, discontinue semaglutide. Treat promptly per standard of care, and monitor until signs and symptoms resolve.[62656] [64637] [66713]

      Semaglutide is contraindicated in patients with a personal or family history of certain types of thyroid cancer, specifically thyroid C-cell tumors such as medullary thyroid carcinoma (MTC), or in patients with multiple endocrine neoplasia syndrome type 2 (MEN 2). Semaglutide has been shown to cause dose-dependent and treatment duration-dependent malignant thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. A statistically significant increase in cancer was observed in rats receiving semaglutide at all dose levels (greater than 2X human exposure). It is unknown whether semaglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans. Cases of MTC in patients treated with liraglutide, another GLP-1 receptor agonist, have been reported in the postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship between MTC and GLP-1 receptor agonist use in humans. In clinical trials, there were 7 reported cases of papillary thyroid carcinoma in patients treated with liraglutide and 1 case in a comparator-treated patient (1.5 vs. 0.5 cases per 1,000 patient-years). Most of these papillary thyroid carcinomas were less than 1 cm in greatest diameter and were diagnosed after thyroidectomy, which was prompted by finding on protocol-specified screening with serum calcitonin or thyroid ultrasound.[38653] Patients should be counseled on the potential risk and symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea or persistent hoarseness). Although routine monitoring of serum calcitonin is of uncertain value in patients treated with semaglutide, if serum calcitonin is measured and found to be elevated, the patient should be referred to an endocrinologist for further evaluation.[62656] [64637] [66713]

      Semaglutide should not be used for the treatment of type 1 diabetes mellitus.[62656] [64637]

      Hypoglycemia should be monitored for by the patient and clinician when semaglutide treatment is initiated and continued for type 2 diabetes mellitus (T2DM) and when used for weight reduction and maintenance. In a clinical trial of semaglutide injection for weight loss (Wegovy) in patients with T2DM and a BMI of 27 kg/m2 or more, hypoglycemia (defined as a plasma glucose less than 54 mg/dL) was reported in 6.2% of semaglutide-treated patients versus 2.5% of placebo-treated patients. One episode of severe hypoglycemia (requiring the assistance of another person) was reported in one semaglutide-treated patient versus no placebo-treated patients. In clinical trials of semaglutide injection for T2DM (Ozempic), hypoglycemia was increased when semaglutide was used in combination with a sulfonylurea; patients receiving semaglutide in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia. Although specific dose recommendations are not available, the clinician should consider a dose reduction of the sulfonylurea or insulin when used in combination with semaglutide.[62656] [64637] [66713] In addition, when semaglutide is used in combination with insulin detemir, the dose of insulin should be evaluated; in patients at increased risk of hypoglycemia consider reducing the dose of insulin at initiation of semaglutide, followed by careful titration.[22300] Adequate blood glucose monitoring should be continued and followed. Patient and family education regarding hypoglycemia management is crucial; the patient and patient's family should be instructed on how to recognize and manage the symptoms of hypoglycemia. Early warning signs of hypoglycemia may be less obvious in patients with hypoglycemia unawareness which can be due to a long history of diabetes (where deficiencies in the release or response to counter regulatory hormones exist), with autonomic neuropathy, intensified diabetes control, or taking beta-blockers, guanethidine, or reserpine. Patients should be aware of the need to have a readily available source of glucose (dextrose, d-glucose) or other carbohydrate to treat hypoglycemic episodes. In severe hypoglycemia, intravenous dextrose or glucagon injections may be needed. Because hypoglycemic events may be difficult to recognize in some elderly patients, antidiabetic agent regimens should be carefully managed to obviate an increased risk of severe hypoglycemia. Severe or frequent hypoglycemia in a patient is an indication for the modification of treatment regimens, including setting higher glycemic goals.[62656] [64926] Semaglutide may have particular benefits when used in patients with T2DM who are overweight. According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, weight loss medications should be considered as an adjunct to lifestyle therapy in all patients with T2DM as needed for weight loss sufficient to improve glycemic control, lipids, and blood pressure.[62881]

      Semaglutide for type 2 diabetes mellitus (T2DM) has not been studied in patients with a history of pancreatitis and there is limited data from clinical trials with semaglutide injection for weight management. It is not known whether these patients are at an increased risk for developing pancreatitis. After initiation and dose increases, patients should be observed carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back and which may or may not be accompanied by vomiting). If pancreatitis is suspected, discontinue semaglutide; if pancreatitis is confirmed, do not resume semaglutide. Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including semaglutide.[62656] [64637] [66713] The FDA and the EMA have stated that after review of published and unpublished reports, the current data do not support an increased risk of pancreatitis and pancreatic cancer in patients receiving incretin mimetics. The agencies have not reached any new conclusions about safety risks of the incretin mimetics, although they have expressed that the totality of the data that have been reviewed provides reassurance. Continue to consider precautions related to pancreatic risk until more data are available.[53573] [56778] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, obese patients receiving incretin-based therapies for weight loss should be monitored for the development of pancreatitis. Incretin-based therapies should be avoided in patients with prior or current pancreatitis; otherwise, there are insufficient data to recommend withholding them for weight loss due to concerns of pancreatitis.[62881]

      Use semaglutide with caution in patients with known gallbladder disease or a history of cholelithiasis. If cholelithiasis or cholecystitis are suspected in a patient taking semaglutide, gallbladder studies are indicated. Acute gallbladder disease events, such as cholecystitis or cholelithiasis, have been reported in clinical studies of patients receiving semaglutide for type 2 diabetes mellitus (T2DM) and for weight management.[62656] [64637] [66713] For weight management, the incidence of cholecystitis or cholelithiasis was higher in subcutaneous semaglutide treated pediatric patients 12 years and older compared to adult patients. Substantial or rapid weight loss can increase the risk of cholelithiasis; however, the incidence of acute gallbladder disease was greater in semaglutide-treated patients than in placebo-treated patients, even after accounting for the degree of weight loss.[66713] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, close monitoring for cholelithiasis is recommended during weight loss therapy, regardless of modality. In high-risk patients, use semaglutide with caution. Effective preventative measures for patients at risk for cholelithiasis include a slower rate of weight loss, increasing/including some dietary fat in the diet (assuming the patient has been on a very low-calorie diet containing little or no fat), or administration of ursodeoxycholic acid.[62881]

      During semaglutide therapy, patients with a history of diabetic retinopathy should be closely monitored. Inform patients to contact their care team if changes in vision are experienced during treatment. There is an increased risk for diabetic retinopathy complications in patients with a history of diabetic retinopathy at baseline compared to patients without a known history of diabetic retinopathy. In a 2-year trial involving patients with type 2 diabetes mellitus (T2DM) and high cardiovascular risk, more events of diabetic retinopathy complications occurred in patients treated with semaglutide 0.5 and 1 mg once weekly injections (3%) compared to placebo (1.8%). The absolute risk increase for diabetic retinopathy complications was larger among patients with a history of diabetic retinopathy at baseline (semaglutide injection 8.2%, placebo 5.2%) than among patients without a known history of diabetic retinopathy (semaglutide injection 0.7%, placebo 0.4%). In a pooled analysis of glycemic control trials with oral semaglutide, diabetic retinopathy complications occurred in 4.2% of T2DM patients receiving semaglutide and 3.8% with comparator. In a trial of semaglutide injection (Wegovy) in patients with T2DM and BMI of 27 kg/m2 or more, diabetic retinopathy was reported by 4% of semaglutide-treated patients vs. 2.7% of placebo-treated patients. Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. The effect of long-term glycemic control with semaglutide on diabetic retinopathy complications has not been studied.[62656] [64637] [66713]

      Use caution during treatment with semaglutide in patients with renal impairment or end-stage renal disease (renal failure); however, no dose adjustments are needed based on renal function. Use caution and monitor renal function when initiating or increasing doses of semaglutide in patients with renal impairment or any patients who report severe gastrointestinal reactions during use. There have been postmarketing reports of renal impairment, acute kidney injury, and worsening of chronic renal failure, which sometimes has required hemodialysis, in patients treated with GLP-1 receptor agonists. Some of these events have been reported in patients without known underlying renal disease. In many of these cases, altered renal function has been reversed with supportive treatment and discontinuation of potentially causative agents. A majority of the reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration.[62656] [64637] [66713]

      Suicidal behavior and ideation have been reported in clinical trials with other incretin mimetics indicated for weight management. Therefore, administer semaglutide with caution in patients with depression and avoid use in patients with a history of suicide attempts or active suicidal ideation; monitor patients for the emergence or worsening of depression, suicidal thoughts or behavior, and any unusual changes in moods or behaviors. Discontinue semaglutide in patients who develop suicidal thoughts or behaviors.[66713] In January 2024, the FDA announced that they have not found evidence that use of GLP-1 RAs for type 2 diabetes or weight management causes suicidal thoughts or actions. During their preliminary evaluation, they conducted detailed reviews of reports of suicidal thoughts or actions received in the FDA Adverse Event Reporting System (FAERS) and reviews of clinical trials, including large outcome studies and observational studies. However, because of the small number of suicidal thoughts or actions observed in both people using GLP-1 RAs and in the comparative control groups, they cannot definitively rule out that a small risk may exist; therefore, FDA is continuing to look into this issue. Further evaluations include a meta-analysis of clinical trials across all GLP-1 RA products and an analysis of postmarketing data in the Sentinel System; final conclusions and recommendations will be communicated once more information is known.[70130] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, all patients undergoing weight loss therapy should be monitored for mood disorders, depression, and suicidal ideation. Caution is recommended in patients with a psychotic disorder (e.g., schizophrenia) due to insufficient data. Patients receiving an antipsychotic should be treated with structured lifestyle modifications to promote weight loss and weight gain prevention; these guidelines suggest that metformin may be beneficial for modest weight loss and metabolic improvements in patients receiving an antipsychotic.[62881]

      Semaglutide (Wegovy) for the treatment of obesity or weight management should not be used during pregnancy because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm due to the potential hazard of maternal weight loss to the fetus. There is a pregnancy exposure registry for women who use semaglutide intended for weight management (Wegovy) during pregnancy. Contact Novo Nordisk at 1-877-390-2760 or www.wegovypregnancyregistry.com for more information.[66713] According to the American Association of Clinical Endocrinologists the and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, weight loss medications must not be used during pregnancy; these guidelines recommend contraception requirements for patients of childbearing potential; those receiving semaglutide for weight reduction should use adequate contraception and discontinue semaglutide if pregnancy occurs.[62881] There are no adequate data or clinical studies of semaglutide use for the treatment of type 2 diabetes mellitus (T2DM) in pregnant women to inform a drug-associated risk for adverse developmental outcomes; use in pregnancy only if the potential benefit justifies the potential risk to the fetus. Rat studies have noted embryofetal mortality, structural abnormalities, and alterations to growth at maternal exposures below the maximum recommended human dose (MRHD) based on exposure AUC. In rabbits and cynomolgus monkeys administered semaglutide during organogenesis, early pregnancy losses and structural abnormalities were observed at below the MRHD (rabbit) and 5-fold or greater the MRHD (monkey). Poorly controlled diabetes during pregnancy also increases fetal risk.[62656] [64637] In addition, salcaprozate sodium (SNAC), an absorption enhancer in oral semaglutide tablets, crosses the placenta, and reaches fetal tissues in rats. In a pre- and postnatal development study of SNAC exposure, an increase in gestation length, an increase in the number of stillbirths, and a decrease in pup viability were observed.[64637] The American College of Obstetricians and Gynecologists (ACOG) and the American Diabetes Association (ADA) continue to recommend human insulin as the standard of care in pregnant women with diabetes mellitus and gestational diabetes mellitus (GDM) requiring medical therapy; insulin does not cross the placenta.[64926] [62358] [62656] [64637]

      Semaglutide may be associated with reproductive risk and preconceptual planning is recommended; females of childbearing potential should discontinue semaglutide at least 2 months before a planned pregnancy due to the drug's long washout period.[62656] [64637] [66713]

      Use injectable semaglutide with caution during lactation; oral semaglutide therapy is not recommended during breast-feeding. There are no data on the presence of semaglutide in human milk, the effects on the breast-fed infant, or the effects on milk production. Semaglutide was present in the milk of lactating rats and was detected at levels 3- to 12- fold lower than in maternal rat plasma.[62656] [64637] [66713] Salcaprozate sodium (SNAC) (an absorption enhancer in oral semaglutide tablets) and/or its metabolites concentrated in the milk of lactating rats. There are no data on the presence of SNAC in human milk. Since the activity of UGT2B7, an enzyme involved in SNAC clearance, is lower in infants compared to adults, higher SNAC plasma levels may occur in neonates and infants. Because of the unknown potential for serious adverse reactions in the breastfed infant due to the possible accumulation of SNAC from breast-feeding and because semaglutide injection can be considered for use during lactation, advise patients that breast-feeding is not recommended during treatment with oral semaglutide tablets.[64637] If semaglutide is discontinued and blood glucose is not controlled on diet and exercise alone, insulin therapy should be considered. Other oral hypoglycemics may be considered as possible alternatives during breast-feeding. Because acarbose has limited systemic absorption, which results in minimal maternal plasma concentrations, clinically significant exposure via breast milk is not expected.[46303] Also, while the manufacturers of metformin recommend against breast-feeding while taking the drug, data have shown that metformin is excreted into breast milk in small amounts and adverse effects on infant plasma glucose have not been reported in human studies.[31407] [31408] [31409] Tolbutamide is usually considered compatible with breast-feeding.[27500] Glyburide may also be a suitable alternative since it was not detected in the breast milk of lactating women who received single and multiple doses of glyburide.[31568] If any oral hypoglycemics are used during breast-feeding, the nursing infant should be monitored for signs of hypoglycemia, such as increased fussiness or somnolence.[46104]

      Safety and efficacy were not different in geriatric adults versus younger adults during semaglutide clinical trials. In general, however, geriatric adults are especially at risk for hypoglycemic episodes.[62656] [64637] [66713] The specific reasons identified include intensive insulin therapy, decreased renal function, severe liver disease, alcohol ingestion, defective counter regulatory hormone release, missing meals/fasting, and gastroparesis. Because hypoglycemic events may be difficult to recognize in some older adults, antidiabetic agent regimens should be carefully managed to obviate an increased risk of severe hypoglycemia. Severe or frequent hypoglycemia is an indication for the modification of treatment regimens, including setting higher glycemic goals.[64926] In a cardiovascular outcomes trial, a higher incidence of hip and pelvis fractures occurred in adults aged 75 years and older treated with semaglutide compared to placebo. Both semaglutide- and placebo-treated adults aged 75 years and older reported more serious adverse reactions overall compared to younger adults.[66713]

      Revision Date: 03/28/2024, 01:48:00 AM

      References

      22300 - Levemir (insulin detemir [rDNA origin]) injection package insert. Princeton, NJ: Novo Nordisk, Inc; 2022 Dec.27500 - American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.31407 - Hale TW, Kristensen JH, Hackett LP, et al. Transfer of metformin into human milk. Diabetologia 2002;45:1509-14.31408 - Gardiner SJ, Kirkpatrick CMJ, Begg EJ, et al. Transfer of metformin into human milk. Clin Pharmacol Ther 2003;73:71-7.31409 - Briggs GG, Ambrose PJ, Nageotte MP, et al. Excretion of metformin into breast milk and the effect on nursing infants. Obstet Gynecol 2005;105:1437-41.31568 - Feig DS, Donat DJ, Briggs GG, et al. Transfer of glyburide and glipizide into breast milk. Diabetes Care 2005;28:1851-5.38653 - Victoza (liraglutide) package insert. Princeton, NJ: Novo Nordisk Inc; 2023 June.46104 - Spencer JP, Gonzalez LS, Barnhart DJ. Medications in the breast-feeding mother. Am Fam Physician 2001; 64:119-126.46303 - Everett J. Use of oral antidiabetic agents during breastfeeding. J Hum Lact 1997;13:319-21.53573 - Food and Drug Administration (US FDA) Drug Medwatch-FDA investigating reports of possible increased risk of pancreatitis and pre-cancerous findings of the pancreas from incretin mimetic drugs for type 2 diabetes. Retrieved Mar. 14, 2013. Available on the World Wide Web at http://www.fda.gov/Drugs/DrugSafety/ucm343187.htm.56778 - Egan AG, Blind E, Dunder K, , et al. Pancreatic safety of incretin-based drugs-FDA and EMA assessment. N Engl J Med 2014;370:794—7.62358 - American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins-Obstetrics. Practice Bulletin No. 190: Gestational Diabetes Mellitus. Obstet Gynecol. 2018;131:e49-e64. Reaffirmed 2019.62656 - Ozempic (semaglutide solution for injection) package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2023 Sept.62881 - Garvey WT, Mechanick JI, Brett EM, et al; Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines. American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract. 2016 Jul;22 Suppl 3:1-203. Epub 2016 May 24.64637 - Rybelsus (semaglutide tablets) package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2024 Jan.64926 - American Diabetes Association. Standards of Medical Care in Diabetes - 2024. Diabetes Care. 2024; 47(Suppl 1):S1-S321. Available at: https://diabetesjournals.org/care/issue/47/Supplement_166713 - Wegovy (semaglutide) injection package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2024 Mar.70130 - US Food and Drug Administration (FDA). FDA Medwatch - Certain Type of Medicines Approved for Type 2 Diabetes and Obesity: Drug Safety Communication - Update on FDA’s Ongoing Evaluation of Reports of Suicidal Thoughts or Actions. Retrieved January 11, 2024. Available on the World Wide Web at: https://www.fda.gov/drugs/drug-safety-and-availability/update-fdas-ongoing-evaluation-reports-suicidal-thoughts-or-actions-patients-taking-certain-type.

      Mechanism of Action

      Semaglutide an incretin mimetic; specifically, semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist with 94% sequence homology to human GLP-1. Semaglutide binds and activates the GLP-1 receptor.[62656][64637] GLP-1 is an important, gut-derived, glucose homeostasis regulator that is released after the oral ingestion of carbohydrates or fats. In patients with type 2 diabetes, GLP-1 concentrations are decreased in response to an oral glucose load. GLP-1 enhances insulin secretion; it increases glucose-dependent insulin synthesis and in vivo secretion of insulin from pancreatic beta cells in the presence of elevated glucose. In addition to increases in insulin secretion and synthesis, GLP-1 suppresses glucagon secretion, slows gastric emptying, reduces food intake, and promotes beta-cell proliferation.[38658] The principal mechanism of protraction resulting in the long half-life of semaglutide is albumin binding, which results in decreased renal clearance and protection from metabolic degradation; semaglutide is stabilized against degradation by the DPP-4 enzyme. Semaglutide reduces blood glucose through a mechanism where it stimulates insulin secretion and lowers glucagon secretion, both in a glucose-dependent manner. Therefore, when blood glucose is high, insulin secretion is stimulated and glucagon secretion is inhibited. The mechanism of blood glucose lowering also involves a minor delay in gastric emptying in the early postprandial phase.[62656][64637]

      GLP-1 is also a physiological regulator of appetite and caloric intake and the GLP-1 receptor is present in several areas of the brain involved in appetite regulation. Semaglutide reduces caloric intake and delays gastric emptying. It lowers body weight with greater fat mass loss than lean mass loss. The exact mechanism of semaglutide for cardiovascular risk reduction has not been established.[66713]

      Revision Date: 03/28/2024, 01:48:00 AM

      References

      38658 - Russell -Jones D, Vaag A, Schmidtz O, et al. Liraglutide vs. insulin glargine and placebo in combination with metformin andsulphonylurea therapy in type 2 diabetes mellitus: a randomised controlled trial (LEAD-5 met + SU). Diabetologia 2009;52:2046-55.62656 - Ozempic (semaglutide solution for injection) package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2023 Sept.64637 - Rybelsus (semaglutide tablets) package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2024 Jan.66713 - Wegovy (semaglutide) injection package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2024 Mar.

      Pharmacokinetics

      Semaglutide is given via subcutaneous or oral administration. The mean estimated volume of distribution is 12.5 L and 8 L following subcutaneous and oral administration; respectively. Semaglutide is more than 99% bound to plasma albumin. The primary route of elimination is metabolism following proteolytic cleavage of the peptide backbone and sequential beta-oxidation of the fatty acid side-chain. The primary excretion routes of semaglutide-related material is via the urine and feces. Approximately 3% of the dose is excreted in the urine as intact semaglutide. The clearance is approximately 0.05 L/hour and 0.04 L/hour following subcutaneous and oral administration; respectively. With an elimination half-life of approximately 1 week, semaglutide will be present in the circulation for about 5 weeks after the last dose and up to 7 weeks after the last dose for the treatment of obesity.[62656][64637][66713]

       

      Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: None

      Route-Specific Pharmacokinetics

      Oral Route

      Semaglutide is co-formulated with salcaprozate sodium which facilitates the absorption of semaglutide after oral administration. The absorption of semaglutide primarily occurs in the stomach. Population pharmacokinetics (PK) estimated semaglutide exposure to increase in a dose-proportional manner. The mean population-PK estimated steady-state concentrations following once daily oral administration of 7 and 14 mg were approximately 6.7 nmol/L and 14.6 nmol/L, respectively. Following oral administration, maximum concentration of semaglutide is reached 1 hour post-dose. Steady-state exposure is achieved following 4 to 5 weeks administration. Population-PK estimated absolute bioavailability of semaglutide is approximately 0.4% to 1%, following oral administration.[64637]

       

      Oral semaglutide tablets are formulated with salcaprozate sodium (SNAC), an absorption enhancer. UGT2B7 is an enzyme involved in SNAC clearance. SNAC crosses the placenta and reaches fetal tissues in rats and SNAC and/or its metabolites concentrated in the milk of lactating rats.[64637]

      Subcutaneous Route

      Following subcutaneous administration, maximum concentrations of semaglutide were attained at 1 to 3 days post-dosing. Similar exposure is achieved with subcutaneous administration of semaglutide in the abdomen, thigh, or upper arm. The absolute bioavailability of subcutaneous semaglutide is 89%.[62656][66713]

      • Ozempic: The mean population estimated steady-state concentrations following once weekly subcutaneous administration of 0.5 mg and 1 mg semaglutide were approximately 65 ng/mL and 123 ng/mL, respectively. Steady-state exposures are achieved following 4 to 5 weeks of once-weekly administration. Exposures at the 0.5 mg and 1 mg dose levels were consistent with a dose-proportional increase. In the trial comparing semaglutide 1 mg and 2 mg, the mean steady state concentrations were 111.1 ng/mL and 222.1 ng/mL, respectively.[62656]
      • Wegovy: The average semaglutide steady-state concentration following subcutaneous administration of semaglutide was approximately 75 nmol/L in patients with either obesity (BMI greater than or equal to 30 kg/m2) or overweight (BMI 27 kg/m2 or more). The steady-state exposure of semaglutide increased proportionally with doses up to 2.4 mg subcutaneously once weekly.[66713]

      Special Populations

      Hepatic Impairment

      Hepatic impairment does not have any impact on the exposure of semaglutide. The pharmacokinetics of semaglutide were evaluated in patients with mild, moderate, and severe hepatic impairment compared with subjects with normal hepatic function in studies with either a single dose of 0.5 mg subcutaneous semaglutide or 10 consecutive days of once-daily semaglutide oral tablets.[62656][64637][66713]

      Renal Impairment

      Renal impairment does not impact the pharmacokinetics of semaglutide in a clinically relevant manner. This was evident in studies with either a single dose of 0.5 mg subcutaneous semaglutide or 10 consecutive days of once-daily oral doses of semaglutide in patients with mild, moderate, severe, and end stage renal disease (ESRD) compared with subjects with normal renal function; this was also shown for subjects with both type 2 diabetes mellitus and renal impairment based on data from clinical studies.[62656][64637][66713]

      Pediatrics

      The pharmacokinetics of semaglutide have not been studied in children.[62656][64637][66713]

      Geriatric

      Age did not significantly affect the pharmacokinetics of semaglutide.[62656][64637][66713]

      Gender Differences

      Gender did not significantly affect the pharmacokinetics of semaglutide.[62656][64637]

      Ethnic Differences

      Race did not significantly affect the pharmacokinetics of semaglutide.[62656][64637][66713]

      Obesity

      In the clinical trials, the exposure of semaglutide exhibited an indirect relationship with an increase in body weight; however, subcutaneous semaglutide doses of 0.5 mg and 1 mg provide adequate systemic exposure over the body weight range of 40 to 198 kg.[62656] Oral doses of 7 mg and 14 mg provide adequate systemic exposure over the body weight range of 40 to 188 kg.[64637]

      Other

      Disease in the upper GI tract (chronic gastritis and/or gastroesophageal reflux disease) does not impact semaglutide pharmacokinetics in a clinically relevant manner; this was shown in a study in patients with type 2 diabetes mellitus with or without upper GI disease given semaglutide oral tablets once daily for 10 consecutive days.[64637]

      Revision Date: 03/28/2024, 01:48:00 AM

      References

      62656 - Ozempic (semaglutide solution for injection) package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2023 Sept.64637 - Rybelsus (semaglutide tablets) package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2024 Jan.66713 - Wegovy (semaglutide) injection package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2024 Mar.

      Pregnancy/Breast-feeding

      pregnancy

      Semaglutide (Wegovy) for the treatment of obesity or weight management should not be used during pregnancy because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm due to the potential hazard of maternal weight loss to the fetus. There is a pregnancy exposure registry for women who use semaglutide intended for weight management (Wegovy) during pregnancy. Contact Novo Nordisk at 1-877-390-2760 or www.wegovypregnancyregistry.com for more information.[66713] According to the American Association of Clinical Endocrinologists the and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, weight loss medications must not be used during pregnancy; these guidelines recommend contraception requirements for patients of childbearing potential; those receiving semaglutide for weight reduction should use adequate contraception and discontinue semaglutide if pregnancy occurs.[62881] There are no adequate data or clinical studies of semaglutide use for the treatment of type 2 diabetes mellitus (T2DM) in pregnant women to inform a drug-associated risk for adverse developmental outcomes; use in pregnancy only if the potential benefit justifies the potential risk to the fetus. Rat studies have noted embryofetal mortality, structural abnormalities, and alterations to growth at maternal exposures below the maximum recommended human dose (MRHD) based on exposure AUC. In rabbits and cynomolgus monkeys administered semaglutide during organogenesis, early pregnancy losses and structural abnormalities were observed at below the MRHD (rabbit) and 5-fold or greater the MRHD (monkey). Poorly controlled diabetes during pregnancy also increases fetal risk.[62656] [64637] In addition, salcaprozate sodium (SNAC), an absorption enhancer in oral semaglutide tablets, crosses the placenta, and reaches fetal tissues in rats. In a pre- and postnatal development study of SNAC exposure, an increase in gestation length, an increase in the number of stillbirths, and a decrease in pup viability were observed.[64637] The American College of Obstetricians and Gynecologists (ACOG) and the American Diabetes Association (ADA) continue to recommend human insulin as the standard of care in pregnant women with diabetes mellitus and gestational diabetes mellitus (GDM) requiring medical therapy; insulin does not cross the placenta.[64926] [62358] [62656] [64637]

      breast-feeding

      Use injectable semaglutide with caution during lactation; oral semaglutide therapy is not recommended during breast-feeding. There are no data on the presence of semaglutide in human milk, the effects on the breast-fed infant, or the effects on milk production. Semaglutide was present in the milk of lactating rats and was detected at levels 3- to 12- fold lower than in maternal rat plasma.[62656] [64637] [66713] Salcaprozate sodium (SNAC) (an absorption enhancer in oral semaglutide tablets) and/or its metabolites concentrated in the milk of lactating rats. There are no data on the presence of SNAC in human milk. Since the activity of UGT2B7, an enzyme involved in SNAC clearance, is lower in infants compared to adults, higher SNAC plasma levels may occur in neonates and infants. Because of the unknown potential for serious adverse reactions in the breastfed infant due to the possible accumulation of SNAC from breast-feeding and because semaglutide injection can be considered for use during lactation, advise patients that breast-feeding is not recommended during treatment with oral semaglutide tablets.[64637] If semaglutide is discontinued and blood glucose is not controlled on diet and exercise alone, insulin therapy should be considered. Other oral hypoglycemics may be considered as possible alternatives during breast-feeding. Because acarbose has limited systemic absorption, which results in minimal maternal plasma concentrations, clinically significant exposure via breast milk is not expected.[46303] Also, while the manufacturers of metformin recommend against breast-feeding while taking the drug, data have shown that metformin is excreted into breast milk in small amounts and adverse effects on infant plasma glucose have not been reported in human studies.[31407] [31408] [31409] Tolbutamide is usually considered compatible with breast-feeding.[27500] Glyburide may also be a suitable alternative since it was not detected in the breast milk of lactating women who received single and multiple doses of glyburide.[31568] If any oral hypoglycemics are used during breast-feeding, the nursing infant should be monitored for signs of hypoglycemia, such as increased fussiness or somnolence.[46104]

      Revision Date: 03/28/2024, 01:48:00 AM

      References

      27500 - American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.31407 - Hale TW, Kristensen JH, Hackett LP, et al. Transfer of metformin into human milk. Diabetologia 2002;45:1509-14.31408 - Gardiner SJ, Kirkpatrick CMJ, Begg EJ, et al. Transfer of metformin into human milk. Clin Pharmacol Ther 2003;73:71-7.31409 - Briggs GG, Ambrose PJ, Nageotte MP, et al. Excretion of metformin into breast milk and the effect on nursing infants. Obstet Gynecol 2005;105:1437-41.31568 - Feig DS, Donat DJ, Briggs GG, et al. Transfer of glyburide and glipizide into breast milk. Diabetes Care 2005;28:1851-5.46104 - Spencer JP, Gonzalez LS, Barnhart DJ. Medications in the breast-feeding mother. Am Fam Physician 2001; 64:119-126.46303 - Everett J. Use of oral antidiabetic agents during breastfeeding. J Hum Lact 1997;13:319-21.62358 - American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins-Obstetrics. Practice Bulletin No. 190: Gestational Diabetes Mellitus. Obstet Gynecol. 2018;131:e49-e64. Reaffirmed 2019.62656 - Ozempic (semaglutide solution for injection) package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2023 Sept.62881 - Garvey WT, Mechanick JI, Brett EM, et al; Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines. American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract. 2016 Jul;22 Suppl 3:1-203. Epub 2016 May 24.64637 - Rybelsus (semaglutide tablets) package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2024 Jan.64926 - American Diabetes Association. Standards of Medical Care in Diabetes - 2024. Diabetes Care. 2024; 47(Suppl 1):S1-S321. Available at: https://diabetesjournals.org/care/issue/47/Supplement_166713 - Wegovy (semaglutide) injection package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2024 Mar.

      Interactions

      Level 2 (Major)

      • Chloroquine

      Level 3 (Moderate)

      • Acebutolol
      • Acetaminophen; Aspirin
      • Acetaminophen; Aspirin, ASA; Caffeine
      • Acetaminophen; Aspirin; Diphenhydramine
      • Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine
      • Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine
      • Acetaminophen; Chlorpheniramine; Phenylephrine
      • Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine
      • Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine
      • Acetaminophen; Dextromethorphan; Phenylephrine
      • Acetaminophen; Dextromethorphan; Pseudoephedrine
      • Acetaminophen; Guaifenesin; Phenylephrine
      • Acetaminophen; Phenylephrine
      • Acetaminophen; Pseudoephedrine
      • Acrivastine; Pseudoephedrine
      • Albuterol; Budesonide
      • Aliskiren; Hydrochlorothiazide, HCTZ
      • Amiloride; Hydrochlorothiazide, HCTZ
      • Aminosalicylate sodium, Aminosalicylic acid
      • Amlodipine; Benazepril
      • Amlodipine; Olmesartan
      • Amlodipine; Valsartan
      • Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ
      • Amoxicillin; Clarithromycin; Omeprazole
      • Amphetamine
      • Amphetamine; Dextroamphetamine
      • Androgens
      • Angiotensin II receptor antagonists
      • Angiotensin-converting enzyme inhibitors
      • Aripiprazole
      • Articaine; Epinephrine
      • Asenapine
      • Aspirin, ASA
      • Aspirin, ASA; Butalbital; Caffeine
      • Aspirin, ASA; Caffeine
      • Aspirin, ASA; Caffeine; Orphenadrine
      • Aspirin, ASA; Carisoprodol; Codeine
      • Aspirin, ASA; Citric Acid; Sodium Bicarbonate
      • Aspirin, ASA; Dipyridamole
      • Aspirin, ASA; Omeprazole
      • Aspirin, ASA; Oxycodone
      • Atazanavir
      • Atazanavir; Cobicistat
      • Atenolol
      • Atenolol; Chlorthalidone
      • atypical antipsychotic
      • Azelastine; Fluticasone
      • Azilsartan
      • Azilsartan; Chlorthalidone
      • Beclomethasone
      • Benazepril
      • Benazepril; Hydrochlorothiazide, HCTZ
      • Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
      • Benzphetamine
      • Beta-blockers
      • Betamethasone
      • Betaxolol
      • Bismuth Subsalicylate
      • Bismuth Subsalicylate; Metronidazole; Tetracycline
      • Bisoprolol
      • Bisoprolol; Hydrochlorothiazide, HCTZ
      • Bortezomib
      • Brexpiprazole
      • Brimonidine; Timolol
      • Brompheniramine; Dextromethorphan; Phenylephrine
      • Brompheniramine; Phenylephrine
      • Brompheniramine; Pseudoephedrine
      • Brompheniramine; Pseudoephedrine; Dextromethorphan
      • Budesonide
      • Budesonide; Formoterol
      • Budesonide; Glycopyrrolate; Formoterol
      • Bupivacaine; Epinephrine
      • Butalbital; Aspirin; Caffeine; Codeine
      • Candesartan
      • Candesartan; Hydrochlorothiazide, HCTZ
      • Captopril
      • Captopril; Hydrochlorothiazide, HCTZ
      • Carbamazepine
      • Cariprazine
      • Carteolol
      • Carvedilol
      • Cetirizine; Pseudoephedrine
      • Chlophedianol; Dexchlorpheniramine; Pseudoephedrine
      • Chlorothiazide
      • Chlorpheniramine; Dextromethorphan; Phenylephrine
      • Chlorpheniramine; Dextromethorphan; Pseudoephedrine
      • Chlorpheniramine; Ibuprofen; Pseudoephedrine
      • Chlorpheniramine; Phenylephrine
      • Chlorpheniramine; Pseudoephedrine
      • Chlorthalidone
      • Choline Salicylate; Magnesium Salicylate
      • Chromium
      • Ciclesonide
      • Ciprofloxacin
      • Clarithromycin
      • Clozapine
      • Codeine; Guaifenesin; Pseudoephedrine
      • Codeine; Phenylephrine; Promethazine
      • Corticosteroids
      • Cortisone
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      • Daclatasvir
      • Danazol
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      • Darunavir; Cobicistat
      • Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
      • Deflazacort
      • Delafloxacin
      • Desloratadine; Pseudoephedrine
      • Dexamethasone
      • Dexbrompheniramine; Pseudoephedrine
      • Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine
      • Dexmethylphenidate
      • Dextroamphetamine
      • Dextromethorphan; Diphenhydramine; Phenylephrine
      • Dextromethorphan; Guaifenesin; Phenylephrine
      • Dextromethorphan; Guaifenesin; Pseudoephedrine
      • Diethylpropion
      • Digoxin
      • Diphenhydramine; Phenylephrine
      • Disopyramide
      • Dobutamine
      • Dopamine
      • Dorzolamide; Timolol
      • Doxapram
      • Elbasvir; Grazoprevir
      • Enalapril, Enalaprilat
      • Enalapril; Hydrochlorothiazide, HCTZ
      • Ephedrine
      • Ephedrine; Guaifenesin
      • Epinephrine
      • Eprosartan
      • Eprosartan; Hydrochlorothiazide, HCTZ
      • Esmolol
      • Esterified Estrogens; Methyltestosterone
      • Fenofibrate
      • Fenofibric Acid
      • Fexofenadine; Pseudoephedrine
      • Fibric acid derivatives
      • Fludrocortisone
      • Flunisolide
      • Fluoxetine
      • Fluticasone
      • Fluticasone; Salmeterol
      • Fluticasone; Umeclidinium; Vilanterol
      • Fluticasone; Vilanterol
      • Formoterol; Mometasone
      • Fosamprenavir
      • Fosinopril
      • Fosinopril; Hydrochlorothiazide, HCTZ
      • Garlic, Allium sativum
      • Gemfibrozil
      • Gemifloxacin
      • Glecaprevir; Pibrentasvir
      • Glimepiride
      • Glipizide
      • Glipizide; Metformin
      • Glyburide
      • Glyburide; Metformin
      • Green Tea
      • Guaifenesin; Phenylephrine
      • Guaifenesin; Pseudoephedrine
      • Hydrochlorothiazide, HCTZ
      • Hydrochlorothiazide, HCTZ; Moexipril
      • Hydrocortisone
      • Hydroxychloroquine
      • Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate
      • Ibuprofen; Pseudoephedrine
      • Iloperidone
      • Indapamide
      • Indinavir
      • Insulin Aspart
      • Insulin Aspart
      • Insulin Aspart; Insulin Aspart Protamine
      • Insulin Degludec
      • Insulin Degludec; Liraglutide
      • Insulin Detemir
      • Insulin Glargine
      • Insulin Glargine; Lixisenatide
      • Insulin Glulisine
      • Insulin Lispro
      • Insulin Lispro
      • Insulin Lispro; Insulin Lispro Protamine
      • Insulin Regular
      • Insulin, Inhaled
      • Irbesartan
      • Irbesartan; Hydrochlorothiazide, HCTZ
      • Isocarboxazid
      • Isoproterenol
      • Labetalol
      • Lanreotide
      • Lansoprazole; Amoxicillin; Clarithromycin
      • Ledipasvir; Sofosbuvir
      • Levobunolol
      • Levofloxacin
      • Levothyroxine
      • Levothyroxine; Liothyronine (Porcine)
      • Levothyroxine; Liothyronine (Synthetic)
      • Lidocaine; Epinephrine
      • Linezolid
      • Liothyronine
      • Lisdexamfetamine
      • Lisinopril
      • Lisinopril; Hydrochlorothiazide, HCTZ
      • Lonapegsomatropin
      • Lopinavir; Ritonavir
      • Loratadine; Pseudoephedrine
      • Lorcaserin
      • Losartan
      • Losartan; Hydrochlorothiazide, HCTZ
      • Lumateperone
      • Lurasidone
      • Mafenide
      • Magnesium Salicylate
      • Mecasermin, Recombinant, rh-IGF-1
      • Methamphetamine
      • Methenamine; Sodium Salicylate
      • Methylphenidate
      • Methylprednisolone
      • Methyltestosterone
      • Metolazone
      • Metoprolol
      • Metoprolol; Hydrochlorothiazide, HCTZ
      • Metyrapone
      • Midodrine
      • Moexipril
      • Mometasone
      • Monoamine oxidase inhibitors
      • Moxifloxacin
      • Nadolol
      • Naproxen; Pseudoephedrine
      • Nebivolol
      • Nebivolol; Valsartan
      • Nelfinavir
      • Niacin, Niacinamide
      • Nirmatrelvir; Ritonavir
      • Norepinephrine
      • Octreotide
      • Ofloxacin
      • Olanzapine
      • Olanzapine; Fluoxetine
      • Olanzapine; Samidorphan
      • Olmesartan
      • Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ
      • Olmesartan; Hydrochlorothiazide, HCTZ
      • Olopatadine; Mometasone
      • Oxandrolone
      • Oxymetholone
      • Paliperidone
      • Pasireotide
      • Pegvisomant
      • Pentamidine
      • Pentoxifylline
      • Perindopril
      • Perindopril; Amlodipine
      • Phendimetrazine
      • Phenelzine
      • Phentermine
      • Phentermine; Topiramate
      • Phenylephrine
      • Phenytoin
      • Pindolol
      • Pioglitazone; Glimepiride
      • Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements)
      • Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved)
      • Prednisolone
      • Prednisone
      • Prilocaine; Epinephrine
      • Promethazine; Phenylephrine
      • Propranolol
      • Protease inhibitors
      • Pseudoephedrine
      • Pseudoephedrine; Triprolidine
      • Quetiapine
      • Quinapril
      • Quinapril; Hydrochlorothiazide, HCTZ
      • Quinolones
      • Racepinephrine
      • Ramipril
      • Regular Insulin
      • Regular Insulin; Isophane Insulin (NPH)
      • Risperidone
      • Ritonavir
      • Sacubitril; Valsartan
      • Salicylates
      • Salsalate
      • Saquinavir
      • Serdexmethylphenidate; Dexmethylphenidate
      • Sofosbuvir
      • Sofosbuvir; Velpatasvir
      • Sofosbuvir; Velpatasvir; Voxilaprevir
      • Somapacitan
      • Somatrogon
      • Somatropin, rh-GH
      • Sotalol
      • Spironolactone; Hydrochlorothiazide, HCTZ
      • Sulfadiazine
      • Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole
      • Sulfasalazine
      • Sulfonamides
      • Sulfonylureas
      • Sympathomimetics
      • Tacrolimus
      • Tegaserod
      • Telmisartan
      • Telmisartan; Amlodipine
      • Telmisartan; Hydrochlorothiazide, HCTZ
      • Testosterone
      • Theophylline, Aminophylline
      • Thiazide diuretics
      • Thyroid hormones
      • Timolol
      • Tipranavir
      • Trandolapril
      • Trandolapril; Verapamil
      • Tranylcypromine
      • Triamcinolone
      • Triamterene; Hydrochlorothiazide, HCTZ
      • Valsartan
      • Valsartan; Hydrochlorothiazide, HCTZ
      • Vitamin B Complex Supplements
      • Vonoprazan; Amoxicillin; Clarithromycin
      • Warfarin
      • Ziprasidone

      Level 4 (Minor)

      • Acetazolamide
      • Bumetanide
      • Carbonic anhydrase inhibitors
      • Chlorpromazine
      • Clonidine
      • Codeine; Promethazine
      • Diazoxide
      • Ethacrynic Acid
      • Ethotoin
      • Fluphenazine
      • Fosphenytoin
      • Furosemide
      • Hydroxyprogesterone
      • Loop diuretics
      • Methazolamide
      • Nicotine
      • Orlistat
      • Perphenazine
      • Perphenazine; Amitriptyline
      • Phenothiazines
      • Prochlorperazine
      • Promethazine
      • Promethazine; Dextromethorphan
      • Thioridazine
      • Torsemide
      • Triamterene
      • Trifluoperazine
      Acebutolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present. [28618] [29403] [30489] [30575] [32916] [53617] [62853] Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29403] [61171] Acetaminophen; Aspirin: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29403] [61171] Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29403] [61171] Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Acetaminophen; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Acetaminophen; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Acetazolamide: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction. [28267] [28294] [57357] Acrivastine; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Albuterol; Budesonide: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [51324] [62853] Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29403] [61171] Amlodipine; Benazepril: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [61325] Amlodipine; Olmesartan: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [32198] [42591] Amlodipine; Valsartan: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [32198] [42591] Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [32198] [42591] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Amoxicillin; Clarithromycin; Omeprazole: (Moderate) The concomitant use of clarithromycin and antidiabetic agents can result in significant hypoglycemia. Careful monitoring of blood glucose is recommended. [28238] Amphetamine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Amphetamine; Dextroamphetamine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Androgens: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together. [33919] [33920] [33921] [33922] [33923] [33924] Angiotensin II receptor antagonists: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [32198] [42591] Angiotensin-converting enzyme inhibitors: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [61325] Aripiprazole: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. [28915] [30575] Articaine; Epinephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Asenapine: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. [28915] [30575] Aspirin, ASA: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29403] [61171] Aspirin, ASA; Butalbital; Caffeine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29403] [61171] Aspirin, ASA; Caffeine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29403] [61171] Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29403] [61171] Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29403] [61171] Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29403] [61171] Aspirin, ASA; Dipyridamole: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29403] [61171] Aspirin, ASA; Omeprazole: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29403] [61171] Aspirin, ASA; Oxycodone: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29403] [61171] Atazanavir: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. [30575] [50113] [50814] Atazanavir; Cobicistat: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. [30575] [50113] [50814] Atenolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present. [28618] [29403] [30489] [30575] [32916] [53617] [62853] Atenolol; Chlorthalidone: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present. [28618] [29403] [30489] [30575] [32916] [53617] [62853] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] atypical antipsychotic: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. [28915] [30575] Azelastine; Fluticasone: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [51324] [62853] Azilsartan: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [32198] [42591] Azilsartan; Chlorthalidone: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [32198] [42591] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Beclomethasone: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [51324] [62853] Benazepril: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [61325] Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [61325] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29403] [61171] Benzphetamine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Beta-blockers: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present. [28618] [29403] [30489] [30575] [32916] [53617] [62853] Betamethasone: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [51324] [62853] Betaxolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present. [28618] [29403] [30489] [30575] [32916] [53617] [62853] Bismuth Subsalicylate: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29403] [61171] Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29403] [61171] Bisoprolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present. [28618] [29403] [30489] [30575] [32916] [53617] [62853] Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present. [28618] [29403] [30489] [30575] [32916] [53617] [62853] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Bortezomib: (Moderate) During clinical trials of bortezomib, hypoglycemia and hyperglycemia were reported in diabetic patients receiving antidiabetic agents. Patients taking antidiabetic agents and receiving bortezomib treatment may require close monitoring of their blood glucose levels and dosage adjustment of their medication. [28383] Brexpiprazole: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. [28915] [30575] Brimonidine; Timolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present. [28618] [29403] [30489] [30575] [32916] [53617] [62853] Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Brompheniramine; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Brompheniramine; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Budesonide: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [51324] [62853] Budesonide; Formoterol: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [51324] [62853] Budesonide; Glycopyrrolate; Formoterol: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [51324] [62853] Bumetanide: (Minor) Loop diuretics, such as bumetanide, furosemide, and torsemide, may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, including incretin mimetics. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated. [28429] [28620] [29353] Bupivacaine; Epinephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29403] [61171] Candesartan: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [32198] [42591] Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [32198] [42591] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Captopril: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [61325] Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [61325] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Carbamazepine: (Moderate) Consider increased clinical or laboratory monitoring for carbamazepine if administered with oral semaglutide as the oral absorption of carbamazepine may be altered. Semaglutide delays gastric emptying and therefore has the potential to affect absorption of other orally administered medications, particularly those with a narrow therapeutic index. Be sure to administer oral semaglutide as directed, separately from other oral medications. This interaction does not occur with subcutaneous semaglutide. [64637] Carbonic anhydrase inhibitors: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction. [28267] [28294] [57357] Cariprazine: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. [28915] [30575] Carteolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present. [28618] [29403] [30489] [30575] [32916] [53617] [62853] Carvedilol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present. [28618] [29403] [30489] [30575] [32916] [53617] [62853] Cetirizine; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Chloroquine: (Major) Careful monitoring of blood glucose is recommended when chloroquine and antidiabetic agents, including the incretin mimetics, are coadministered. A decreased dose of the antidiabetic agent may be necessary as severe hypoglycemia has been reported in patients treated concomitantly with chloroquine and an antidiabetic agent. [29758] Chlorothiazide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Chlorpheniramine; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Chlorpheniramine; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Chlorpromazine: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. [28915] [30575] Chlorthalidone: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Choline Salicylate; Magnesium Salicylate: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29403] [61171] Chromium: (Moderate) Chromium dietary supplements may lower blood glucose. As part of the glucose tolerance factor molecule, chromium appears to facilitate the binding of insulin to insulin receptors in tissues and to aid in glucose metabolism. Because blood glucose may be lowered by the use of chromium, patients who are on antidiabetic agents may need dose adjustments. Close monitoring of blood glucose is recommended. [25731] [25732] Ciclesonide: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [51324] [62853] Ciprofloxacin: (Moderate) Monitor blood glucose during concomitant incretin mimetic and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [28423] [28424] [43411] [62028] [65562] Clarithromycin: (Moderate) The concomitant use of clarithromycin and antidiabetic agents can result in significant hypoglycemia. Careful monitoring of blood glucose is recommended. [28238] Clonidine: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients. [29533] [30585] [44086] Clozapine: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. [28915] [30575] Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Codeine; Phenylephrine; Promethazine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. [28915] [30575] Codeine; Promethazine: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. [28915] [30575] Corticosteroids: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [51324] [62853] Cortisone: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [51324] [62853] Cyclosporine: (Moderate) Consider increased clinical or laboratory monitoring for oral cyclosporine administered with oral semaglutide as the absorption of cyclosporine may be altered. Semaglutide delays gastric emptying and therefore has the potential to affect absorption of other orally administered medications. Be sure to administer oral semaglutide as directed, separately from other oral medications. This absorption interaction does not occur with subcutaneous semaglutide or IV cyclosporine. Patients should also be monitored for worsening of glycemic control when any form of systemic cyclosporine is initiated in patients receiving antidiabetic agents, including semaglutide. Cyclosporine has been reported to cause hyperglycemia. Cyclosporine may have direct beta-cell toxicity and the effects may be dose-related. [30576] [30585] [62853] [64637] Daclatasvir: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir. [60001] Danazol: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together. [33919] [33920] [33921] [33922] [33923] [33924] Darunavir: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. [30575] [50113] [50814] Darunavir; Cobicistat: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. [30575] [50113] [50814] Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. [30575] [50113] [50814] Deflazacort: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [51324] [62853] Delafloxacin: (Moderate) Monitor blood glucose during concomitant incretin mimetic and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [28423] [28424] [43411] [62028] [65562] Desloratadine; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Dexamethasone: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [51324] [62853] Dexbrompheniramine; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Dexmethylphenidate: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Dextroamphetamine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Diazoxide: (Minor) Diazoxide, when administered intravenously or orally, produces a prompt dose-related increase in blood glucose level, due primarily to an inhibition of insulin release from the pancreas, and also to an extrapancreatic effect. The hyperglycemic effect begins within an hour and generally lasts no more than 8 hours in the presence of normal renal function. The hyperglycemic effect of diazoxide is expected to be antagonized by certain antidiabetic agents (e.g., insulin or a sulfonylurea). Blood glucose should be closely monitored. [49068] Diethylpropion: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Digoxin: (Moderate) Consider increased clinical or laboratory monitoring for digoxin if administered with oral semaglutide as the oal absorption of digoxin may be altered. Semaglutide delays gastric emptying and therefore has the potential to affect absorption of other orally administered medications. Be sure to administer oral semaglutide as directed, separately from other oral medications. This interaction does not occur with subcutaneous semaglutide or IV digoxin. [64637] Diphenhydramine; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Disopyramide: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving this combination should be monitored for changes in glycemic control. [28228] Dobutamine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Dopamine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Dorzolamide; Timolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present. [28618] [29403] [30489] [30575] [32916] [53617] [62853] Doxapram: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Elbasvir; Grazoprevir: (Moderate) Closely monitor blood glucose levels if elbasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as elbasvir. [60523] Enalapril, Enalaprilat: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [61325] Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [61325] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Ephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Ephedrine; Guaifenesin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Epinephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Eprosartan: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [32198] [42591] Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [32198] [42591] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Esmolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present. [28618] [29403] [30489] [30575] [32916] [53617] [62853] Esterified Estrogens; Methyltestosterone: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together. [33919] [33920] [33921] [33922] [33923] [33924] Ethacrynic Acid: (Minor) Loop diuretics, such as bumetanide, furosemide, and torsemide, may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, including incretin mimetics. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated. [28429] [28620] [29353] Ethotoin: (Minor) Ethotoin can decrease the hypoglycemic effects of incretin mimetics by producing an increase in blood glucose levels. Patients receiving incretin mimetics should be closely monitored for signs indicating loss of diabetic control when therapy with a hydantoin is instituted. Conversely, patients should be closely monitored for signs of hypoglycemia when therapy with a hydantoin is discontinued. [23813] Fenofibrate: (Moderate) Monitor blood glucose during concomitant incretin mimetic and fibric acid derivative use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [30585] [62853] Fenofibric Acid: (Moderate) Monitor blood glucose during concomitant incretin mimetic and fibric acid derivative use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [30585] [62853] Fexofenadine; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Fibric acid derivatives: (Moderate) Monitor blood glucose during concomitant incretin mimetic and fibric acid derivative use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [30585] [62853] Fludrocortisone: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [51324] [62853] Flunisolide: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [51324] [62853] Fluoxetine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and fluoxetine use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [30585] [32127] [44058] [44059] Fluphenazine: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. [28915] [30575] Fluticasone: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [51324] [62853] Fluticasone; Salmeterol: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [51324] [62853] Fluticasone; Umeclidinium; Vilanterol: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [51324] [62853] Fluticasone; Vilanterol: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [51324] [62853] Formoterol; Mometasone: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [51324] [62853] Fosamprenavir: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. [30575] [50113] [50814] Fosinopril: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [61325] Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [61325] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Fosphenytoin: (Minor) Fosphenytoin can decrease the hypoglycemic effects of incretin mimetics by producing an increase in blood glucose levels. Patients receiving incretin mimetics should be closely monitored for signs indicating loss of diabetic control when therapy with a hydantoin is instituted. Conversely, patients should be closely monitored for signs of hypoglycemia when therapy with a hydantoin is discontinued. [23813] Furosemide: (Minor) Loop diuretics, such as bumetanide, furosemide, and torsemide, may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, including incretin mimetics. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated. [28429] [28620] [29353] Garlic, Allium sativum: (Moderate) Patients receiving antidiabetic agents should use dietary supplements of Garlic, Allium sativum with caution. Constituents in garlic might have some antidiabetic activity, and may increase serum insulin levels and increase glycogen storage in the liver. Monitor blood glucose and glycemic control. Patients with diabetes should inform their health care professionals of their intent to ingest garlic dietary supplements. Some patients may require adjustment to their hypoglycemic medications over time. One study stated that additional garlic supplementation (0.05 to 1.5 grams PO per day) contributed to improved blood glucose control in patients with type 2 diabetes mellitus within 1 to 2 weeks, and had positive effects on total cholesterol and high/low density lipoprotein regulation over time. It is unclear if hemoglobin A1C is improved or if improvements are sustained with continued treatment beyond 24 weeks. Other reviews suggest that garlic may provide modest improvements in blood lipids, but few studies demonstrate decreases in blood glucose in diabetic and non-diabetic patients. More controlled trials are needed to discern if garlic has an effect on blood glucose in patients with diabetes. When garlic is used in foods or as a seasoning, or at doses of 50 mg/day or less, it is unlikely that blood glucose levels are affected to any clinically significant degree. [28464] [28465] [28466] [57571] [63042] [63043] Gemfibrozil: (Moderate) Monitor blood glucose during concomitant incretin mimetic and fibric acid derivative use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [30585] [62853] Gemifloxacin: (Moderate) Monitor blood glucose during concomitant incretin mimetic and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [28423] [28424] [43411] [62028] [65562] Glecaprevir; Pibrentasvir: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. [62201] (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir. [62201] Glimepiride: (Moderate) Monitor blood glucose during concomitant sulfonylurea and semaglutide use; consider decreasing the sulfonylurea dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [62656] [64637] Glipizide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and semaglutide use; consider decreasing the sulfonylurea dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [62656] [64637] Glipizide; Metformin: (Moderate) Monitor blood glucose during concomitant sulfonylurea and semaglutide use; consider decreasing the sulfonylurea dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [62656] [64637] Glyburide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and semaglutide use; consider decreasing the sulfonylurea dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [62656] [64637] Glyburide; Metformin: (Moderate) Monitor blood glucose during concomitant sulfonylurea and semaglutide use; consider decreasing the sulfonylurea dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [62656] [64637] Green Tea: (Moderate) Green tea catechins have been shown to decrease serum glucose concentrations in vitro. Patients with diabetes mellitus taking incretin mimetics should be monitored closely for hypoglycemia if consuming green tea. [29904] [29905] Guaifenesin; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [61325] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Hydrocortisone: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [51324] [62853] Hydroxychloroquine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and hydroxychloroquine use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Hydroxyprogesterone: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [30585] [43316] [62853] [62893] Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29403] [61171] Ibuprofen; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Iloperidone: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. [28915] [30575] Indapamide: (Moderate) A potential pharmacodynamic interaction exists between indapamide and antidiabetic agents, like incretin mimetics. Indapamide can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. [29403] [48959] Indinavir: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. [30575] [50113] [50814] Insulin Aspart: (Moderate) Monitor blood glucose during concomitant insulin aspart and semaglutide use; consider decreasing the insulin aspart dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [62656] [64637] Insulin Aspart: (Moderate) Monitor blood glucose during concomitant insulin aspart and semaglutide use; consider decreasing the insulin aspart dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [62656] [64637] Insulin Aspart; Insulin Aspart Protamine: (Moderate) Monitor blood glucose during concomitant insulin aspart and semaglutide use; consider decreasing the insulin aspart dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [62656] [64637] Insulin Degludec: (Moderate) Monitor blood glucose during concomitant insulin degludec and semaglutide use; consider decreasing the insulin degludec dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [62656] [64637] Insulin Degludec; Liraglutide: (Moderate) Monitor blood glucose during concomitant insulin degludec and semaglutide use; consider decreasing the insulin degludec dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [62656] [64637] Insulin Detemir: (Moderate) Monitor blood glucose during concomitant insulin detemir and semaglutide use; consider decreasing the insulin detemir dose when starting semaglutide. The recommended starting dose of insulin detemir is 10 units/day in persons with type 2 diabetes mellitus inadequately controlled with a glucagon-like peptide-1 (GLP-1) receptor agonist. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [22300] [62656] [64637] Insulin Glargine: (Moderate) Monitor blood glucose during concomitant insulin glargine and semaglutide use; consider decreasing the insulin glargine dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [62656] [64637] Insulin Glargine; Lixisenatide: (Moderate) Monitor blood glucose during concomitant insulin glargine and semaglutide use; consider decreasing the insulin glargine dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [62656] [64637] Insulin Glulisine: (Moderate) Monitor blood glucose during concomitant insulin glulisine and semaglutide use; consider decreasing the insulin glulisine dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [62656] [64637] Insulin Lispro: (Moderate) Monitor blood glucose during concomitant insulin lispro and semaglutide use; consider decreasing the insulin lispro dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [62656] [64637] Insulin Lispro: (Moderate) Monitor blood glucose during concomitant insulin lispro and semaglutide use; consider decreasing the insulin lispro dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [62656] [64637] Insulin Lispro; Insulin Lispro Protamine: (Moderate) Monitor blood glucose during concomitant insulin lispro and semaglutide use; consider decreasing the insulin lispro dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [62656] [64637] Insulin Regular: (Moderate) Monitor blood glucose during concomitant regular insulin and semaglutide use; consider decreasing the regular insulin dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [62656] [64637] Insulin, Inhaled: (Moderate) Monitor blood glucose during concomitant insulin and semaglutide use; consider decreasing the insulin dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [62656] [64637] Irbesartan: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [32198] [42591] Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [32198] [42591] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Isocarboxazid: (Moderate) Monitor blood glucose during concomitant incretin mimetic and monoamine oxidase inhibitor (MAOI) use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29656] [30585] [59433] Isoproterenol: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Labetalol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present. [28618] [29403] [30489] [30575] [32916] [53617] [62853] Lanreotide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia. [33519] Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) The concomitant use of clarithromycin and antidiabetic agents can result in significant hypoglycemia. Careful monitoring of blood glucose is recommended. [28238] Ledipasvir; Sofosbuvir: (Moderate) Closely monitor blood glucose levels if ledipasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agent(s) may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as ledipasvir. [56528] [58167] (Moderate) Closely monitor blood glucose levels if sofosbuvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as sofosbuvir. [56528] Levobunolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present. [28618] [29403] [30489] [30575] [32916] [53617] [62853] Levofloxacin: (Moderate) Monitor blood glucose during concomitant incretin mimetic and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [28423] [28424] [43411] [62028] [65562] Levothyroxine: (Moderate) Consider additional thyroid function monitoring during concomitant use of oral thyroid hormones and oral semaglutide. Advise patients to take oral semaglutide 30 minutes before other oral medications. Concomitant use has been observed to increase levothyroxine exposure by 33% which may increase the risk for symptoms of hyperthyroidism or require a dosage adjustment. Semaglutide delays gastric emptying which may affect the absorption of other orally administered medications. This absorption interaction is not expected with subcutaneous semaglutide or intravenous levothyroxine. Additionally, levothyroxine may worsen glycemic control in patients with diabetes. [43942] [64637] Levothyroxine; Liothyronine (Porcine): (Moderate) Consider additional thyroid function monitoring during concomitant use of oral thyroid hormones and oral semaglutide. Advise patients to take oral semaglutide 30 minutes before other oral medications. Concomitant use has been observed to increase levothyroxine exposure by 33% which may increase the risk for symptoms of hyperthyroidism or require a dosage adjustment. Semaglutide delays gastric emptying which may affect the absorption of other orally administered medications. This absorption interaction is not expected with subcutaneous semaglutide or intravenous levothyroxine. Additionally, levothyroxine may worsen glycemic control in patients with diabetes. [43942] [64637] Levothyroxine; Liothyronine (Synthetic): (Moderate) Consider additional thyroid function monitoring during concomitant use of oral thyroid hormones and oral semaglutide. Advise patients to take oral semaglutide 30 minutes before other oral medications. Concomitant use has been observed to increase levothyroxine exposure by 33% which may increase the risk for symptoms of hyperthyroidism or require a dosage adjustment. Semaglutide delays gastric emptying which may affect the absorption of other orally administered medications. This absorption interaction is not expected with subcutaneous semaglutide or intravenous levothyroxine. Additionally, levothyroxine may worsen glycemic control in patients with diabetes. [43942] [64637] Lidocaine; Epinephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Linezolid: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents. [28599] Liothyronine: (Moderate) Consider additional thyroid function monitoring during concomitant use of oral thyroid hormones and oral semaglutide. Advise patients to take oral semaglutide 30 minutes before other oral medications. Concomitant use has been observed to increase levothyroxine exposure by 33% which may increase the risk for symptoms of hyperthyroidism or require a dosage adjustment. Semaglutide delays gastric emptying which may affect the absorption of other orally administered medications. This absorption interaction is not expected with subcutaneous semaglutide or intravenous levothyroxine. Additionally, levothyroxine may worsen glycemic control in patients with diabetes. [43942] [64637] Lisdexamfetamine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Lisinopril: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [61325] Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [61325] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Lonapegsomatropin: (Moderate) Patients with diabetes mellitus should be monitored closely during somatropin (recombinant rhGH) therapy. Antidiabetic drugs (e.g., insulin or oral agents) may require adjustment when somatropin therapy is instituted in these patients. Growth hormones, such as somatropin, may decrease insulin sensitivity, leading to glucose intolerance and loss of blood glucose control. Therefore, glucose levels should be monitored periodically in all patients treated with somatropin, especially in those with risk factors for diabetes mellitus. [30059] [33527] [45044] [45045] [49770] [56647] [56648] [56649] [56650] [56651] [58095] [59579] [60682] Loop diuretics: (Minor) Loop diuretics, such as bumetanide, furosemide, and torsemide, may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, including incretin mimetics. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated. [28429] [28620] [29353] Lopinavir; Ritonavir: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. [30575] [50113] [50814] Loratadine; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Lorcaserin: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin. [51065] Losartan: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [32198] [42591] Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [32198] [42591] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Lumateperone: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. [28915] [30575] Lurasidone: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. [28915] [30575] Mafenide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29536] [30585] [30623] [32166] [43888] Magnesium Salicylate: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29403] [61171] Mecasermin, Recombinant, rh-IGF-1: (Moderate) Use caution in combining mecasermin, recombinant, rh-IGF-1 or mecasermin rinfabate (rh-IGF-1/rh-IGFBP-3) with antidiabetic agents. Patients should be advised to eat within 20 minutes of mecasermin administration. Glucose monitoring is important when initializing or adjusting mecasermin therapies, when adjusting concomitant antidiabetic therapy, and in the event of hypoglycemic symptoms. An increased risk for hypoglycemia is possible. The hypoglycemic effect induced by IGF-1 activity may be exacerbated. The amino acid sequence of mecasermin (rh-IGF-1) is approximately 50 percent homologous to insulin and cross binding with either receptor is possible. Treatment with mecasermin has been shown to improve insulin sensitivity and to improve glycemic control in patients with either Type 1 or Type 2 diabetes mellitus when used alone or in conjunction with insulins. [31516] [31524] [31821] Methamphetamine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Methazolamide: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction. [28267] [28294] [57357] Methenamine; Sodium Salicylate: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29403] [61171] Methylphenidate: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Methylprednisolone: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [51324] [62853] Methyltestosterone: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together. [33919] [33920] [33921] [33922] [33923] [33924] Metolazone: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Metoprolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present. [28618] [29403] [30489] [30575] [32916] [53617] [62853] Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present. [28618] [29403] [30489] [30575] [32916] [53617] [62853] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Metyrapone: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified. [33528] Midodrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Moexipril: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [61325] Mometasone: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [51324] [62853] Monoamine oxidase inhibitors: (Moderate) Monitor blood glucose during concomitant incretin mimetic and monoamine oxidase inhibitor (MAOI) use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29656] [30585] [59433] Moxifloxacin: (Moderate) Monitor blood glucose during concomitant incretin mimetic and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [28423] [28424] [43411] [62028] [65562] Nadolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present. [28618] [29403] [30489] [30575] [32916] [53617] [62853] Naproxen; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Nebivolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present. [28618] [29403] [30489] [30575] [32916] [53617] [62853] Nebivolol; Valsartan: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present. [28618] [29403] [30489] [30575] [32916] [53617] [62853] (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [32198] [42591] Nelfinavir: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. [30575] [50113] [50814] Niacin, Niacinamide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. [29194] Nicotine: (Minor) Monitor blood glucose concentrations for needed antidiabetic agent dosage adjustments in diabetic patients whenever a change in either nicotine intake or smoking status occurs. Nicotine activates neuroendocrine pathways (e.g., increases in circulating cortisol and catecholamine levels) and may increase plasma glucose. Tobacco smoking is known to aggravate insulin resistance. Cessation of nicotine therapy or tobacco smoking may result in a decrease in blood glucose. [29535] Nirmatrelvir; Ritonavir: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. [30575] [50113] [50814] Norepinephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Octreotide: (Moderate) Monitor patients receiving octreotide concomitantly with insulin or other antidiabetic agents for changes in glycemic control and adjust doses of these medications accordingly. Octreotide alters the balance between the counter-regulatory hormones of insulin, glucagon, and growth hormone, which may result in hypoglycemia or hyperglycemia. The hypoglycemia or hyperglycemia which occurs during octreotide acetate therapy is usually mild but may result in overt diabetes mellitus or necessitate dose changes in insulin or other hypoglycemic agents. In patients with concomitant type1 diabetes mellitus, octreotide is likely to affect glucose regulation, and insulin requirements may be reduced. Symptomatic hypoglycemia, which may be severe, has been reported in type 1 diabetic patients. In Type 2 diabetes patients with partially intact insulin reserves, octreotide administration may result in decreases in plasma insulin levels and hyperglycemia. [29113] [51310] Ofloxacin: (Moderate) Monitor blood glucose during concomitant incretin mimetic and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [28423] [28424] [43411] [62028] [65562] Olanzapine: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. [28915] [30575] Olanzapine; Fluoxetine: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. [28915] [30575] (Moderate) Monitor blood glucose during concomitant incretin mimetic and fluoxetine use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [30585] [32127] [44058] [44059] Olanzapine; Samidorphan: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. [28915] [30575] Olmesartan: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [32198] [42591] Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [32198] [42591] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [32198] [42591] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Olopatadine; Mometasone: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [51324] [62853] Orlistat: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated. [25616] [27971] [60877] [62881] Oxandrolone: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together. [33919] [33920] [33921] [33922] [33923] [33924] Oxymetholone: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together. [33919] [33920] [33921] [33922] [33923] [33924] Paliperidone: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. [28915] [30575] Pasireotide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia. [52611] [58639] Pegvisomant: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pegvisomant treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pegvisomant increases sensitivity to insulin by lowering the activity of growth hormone, and in some patients glucose tolerance improves with treatment. Patients with diabetes treated with pegvisomant and antidiabetic agents may be more likely to experience hypoglycemia. [51250] Pentamidine: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine. [28879] Pentoxifylline: (Moderate) Pentoxiphylline has been used concurrently with antidiabetic agents without observed problems, but it may enhance the hypoglycemic action of antidiabetic agents. Patients should be monitored for changes in glycemic control while receiving pentoxifylline in combination with antidiabetic agents. [6316] [7238] Perindopril: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [61325] Perindopril; Amlodipine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [61325] Perphenazine: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. [28915] [30575] Perphenazine; Amitriptyline: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. [28915] [30575] Phendimetrazine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Phenelzine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and monoamine oxidase inhibitor (MAOI) use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29656] [30585] [59433] Phenothiazines: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. [28915] [30575] Phentermine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Phentermine; Topiramate: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Phenytoin: (Moderate) Consider increased clinical or laboratory monitoring for oral phenytoin administered with oral semaglutide as the absorption of phenytoin may be altered. Semaglutide delays gastric emptying and therefore has the potential to affect absorption of other orally administered medications. Be sure to administer oral semaglutide as directed, separately from other oral medications. This absorption interaction does not occur with subcutaneous semaglutide or IV phenytoin. Patients should also be monitored for worsening of glycemic control when any form of systemic phenytoin is initiated in patients receiving antidiabetic agents, including semaglutide. Phenytoin has been reported to cause hyperglycemia. [23813] [64637] Pindolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present. [28618] [29403] [30489] [30575] [32916] [53617] [62853] Pioglitazone; Glimepiride: (Moderate) Monitor blood glucose during concomitant sulfonylurea and semaglutide use; consider decreasing the sulfonylurea dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [62656] [64637] Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together. [33919] [33920] [33921] [33922] [33923] [33924] Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together. [33919] [33920] [33921] [33922] [33923] [33924] Prednisolone: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [51324] [62853] Prednisone: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [51324] [62853] Prilocaine; Epinephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Prochlorperazine: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. [28915] [30575] Promethazine: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. [28915] [30575] Promethazine; Dextromethorphan: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. [28915] [30575] Promethazine; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. [28915] [30575] Propranolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present. [28618] [29403] [30489] [30575] [32916] [53617] [62853] Protease inhibitors: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. [30575] [50113] [50814] Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Pseudoephedrine; Triprolidine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Quetiapine: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. [28915] [30575] Quinapril: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [61325] Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [61325] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Quinolones: (Moderate) Monitor blood glucose during concomitant incretin mimetic and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [28423] [28424] [43411] [62028] [65562] Racepinephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Ramipril: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [61325] Regular Insulin: (Moderate) Monitor blood glucose during concomitant regular insulin and semaglutide use; consider decreasing the regular insulin dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [62656] [64637] Regular Insulin; Isophane Insulin (NPH): (Moderate) Monitor blood glucose during concomitant insulin NPH and semaglutide use; consider decreasing the insulin NPH dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [62656] [64637] (Moderate) Monitor blood glucose during concomitant regular insulin and semaglutide use; consider decreasing the regular insulin dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [62656] [64637] Risperidone: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. [28915] [30575] Ritonavir: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. [30575] [50113] [50814] Sacubitril; Valsartan: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [32198] [42591] Salicylates: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29403] [61171] Salsalate: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29403] [61171] Saquinavir: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. [30575] [50113] [50814] Serdexmethylphenidate; Dexmethylphenidate: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Sofosbuvir: (Moderate) Closely monitor blood glucose levels if sofosbuvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as sofosbuvir. [56528] Sofosbuvir; Velpatasvir: (Moderate) Closely monitor blood glucose levels if sofosbuvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as sofosbuvir. [56528] (Moderate) Closely monitor blood glucose levels if velpatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as velpatasvir. [56528] [60911] Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Closely monitor blood glucose levels if sofosbuvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as sofosbuvir. [56528] (Moderate) Closely monitor blood glucose levels if velpatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as velpatasvir. [56528] [60911] (Moderate) Closely monitor blood glucose levels if voxilaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as voxilaprevir. [62131] Somapacitan: (Moderate) Patients with diabetes mellitus should be monitored closely during somapacitan therapy. Antidiabetic drugs (e.g., insulin or oral agents) may require adjustment when somapacitan therapy is instituted in these patients. Growth hormones, such as somapacitan, may decrease insulin sensitivity, leading to glucose intolerance and loss of blood glucose control. Therefore, glucose levels should be monitored periodically in all patients treated with somapacitan, especially in those with risk factors for diabetes mellitus. [65878] Somatrogon: (Moderate) Monitor for loss of glycemic control if concomitant use of somatrogon and antidiabetic drugs is necessary; a dose adjustment of the antidiabetic drug may be needed. Growth hormones, such as somatrogon, may decrease insulin sensitivity, leading to glucose intolerance and loss of blood glucose control. [69144] Somatropin, rh-GH: (Moderate) Patients with diabetes mellitus should be monitored closely during somatropin (recombinant rhGH) therapy. Antidiabetic drugs (e.g., insulin or oral agents) may require adjustment when somatropin therapy is instituted in these patients. Growth hormones, such as somatropin, may decrease insulin sensitivity, leading to glucose intolerance and loss of blood glucose control. Therefore, glucose levels should be monitored periodically in all patients treated with somatropin, especially in those with risk factors for diabetes mellitus. [30059] [33527] [45044] [45045] [49770] [56647] [56648] [56649] [56650] [56651] [58095] [59579] [60682] Sotalol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present. [28618] [29403] [30489] [30575] [32916] [53617] [62853] Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Sulfadiazine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29536] [30585] [30623] [32166] [43888] Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Monitor blood glucose during concomitant incretin mimetic and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29536] [30585] [30623] [32166] [43888] Sulfasalazine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29536] [30585] [30623] [32166] [43888] Sulfonamides: (Moderate) Monitor blood glucose during concomitant incretin mimetic and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29536] [30585] [30623] [32166] [43888] Sulfonylureas: (Moderate) Monitor blood glucose during concomitant sulfonylurea and semaglutide use; consider decreasing the sulfonylurea dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [62656] [64637] Sympathomimetics: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Tacrolimus: (Moderate) Consider increased clinical or laboratory monitoring for oral tacrolimus administered with oral semaglutide as the absorption of tacrolimus may be altered. Semaglutide delays gastric emptying and therefore has the potential to affect absorption of other orally administered medications. Be sure to administer oral semaglutide as directed, separately from other oral medications. This absorption interaction does not occur with subcutaneous semaglutide or IV tacrolimus. Patients should also be monitored for worsening of glycemic control when any form of systemic tacrolimus is initiated in patients receiving antidiabetic agents, including semaglutide. Tacrolimus has been reported to cause hyperglycemia. The mechanism of hyperglycemia is thought to be through direct beta-cell toxicity. [30576] [30585] [64637] Tegaserod: (Moderate) Tegaserod can enhance gastric emptying in patients with diabetes. Typically, blood glucose could be affected, which, in turn, may affect the clinical response to antidiabetic agents. However, incretin mimetics have been shown to slow gastric emptying. The clinical effects of these competing mechanisms is not known. The dosing of antidiabetic agents may require adjustment and blood glucose should be closely monitored when coadministered with tegaserod. [28956] [61024] Telmisartan: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [32198] [42591] Telmisartan; Amlodipine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [32198] [42591] Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [32198] [42591] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Testosterone: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together. [33919] [33920] [33921] [33922] [33923] [33924] Theophylline, Aminophylline: (Moderate) Consider increased clinical or laboratory monitoring for aminophylline if administered with oral semaglutide as the absorption of aminophylline may be altered. Semaglutide delays gastric emptying and therefore has the potential to affect absorption of other orally administered medications, particularly those with a narrow therapeutic index, such as aminophylline, a prodrug for theophylline. Administer oral semaglutide separately from other oral medications. Monitor theophylline levels as clinically indicated. This interaction does not occur with subcutaneous semaglutide or with IV aminophylline. [64637] (Moderate) Consider increased clinical or laboratory monitoring for theophylline if administered with oral semaglutide as the absorption of theophylline may be altered. Semaglutide delays gastric emptying and therefore has the potential to affect absorption of other orally administered medications, particularly those with a narrow therapeutic index, such as theophylline. Administer oral semaglutide separately from other oral medications. Monitor theophylline levels as clinically indicated. This interaction does not occur with subcutaneous semaglutide or with IV theophylline. [64637] Thiazide diuretics: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Thioridazine: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. [28915] [30575] Thyroid hormones: (Moderate) Consider additional thyroid function monitoring during concomitant use of oral thyroid hormones and oral semaglutide. Advise patients to take oral semaglutide 30 minutes before other oral medications. Concomitant use has been observed to increase levothyroxine exposure by 33% which may increase the risk for symptoms of hyperthyroidism or require a dosage adjustment. Semaglutide delays gastric emptying which may affect the absorption of other orally administered medications. This absorption interaction is not expected with subcutaneous semaglutide or intravenous levothyroxine. Additionally, levothyroxine may worsen glycemic control in patients with diabetes. [43942] [64637] Timolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present. [28618] [29403] [30489] [30575] [32916] [53617] [62853] Tipranavir: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. [30575] [50113] [50814] Torsemide: (Minor) Loop diuretics, such as bumetanide, furosemide, and torsemide, may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, including incretin mimetics. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated. [28429] [28620] [29353] Trandolapril: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [61325] Trandolapril; Verapamil: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [61325] Tranylcypromine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and monoamine oxidase inhibitor (MAOI) use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [29656] [30585] [59433] Triamcinolone: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [51324] [62853] Triamterene: (Minor) Triamterene can decrease the hypoglycemic effects of antidiabetic agents, such as incretin mimetics, by producing an increase in blood glucose levels. Patients on antidiabetics should be monitored for changes in blood glucose control if triamterene is added or deleted. Dosage adjustments may be necessary. [29160] [29403] [30489] Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] (Minor) Triamterene can decrease the hypoglycemic effects of antidiabetic agents, such as incretin mimetics, by producing an increase in blood glucose levels. Patients on antidiabetics should be monitored for changes in blood glucose control if triamterene is added or deleted. Dosage adjustments may be necessary. [29160] [29403] [30489] Trifluoperazine: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. [28915] [30575] Valsartan: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [32198] [42591] Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [32198] [42591] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Vitamin B Complex Supplements: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. [29194] Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) The concomitant use of clarithromycin and antidiabetic agents can result in significant hypoglycemia. Careful monitoring of blood glucose is recommended. [28238] Warfarin: (Moderate) Consider additional warfarin monitoring during concomitant use of oral semaglutide. Oral semaglutide delays gastric emptying and has been observed to increase warfarin overall exposure. Advise patients to take oral semaglutide 30 minutes before other oral medications. This interaction is not expected with subcutaneous semaglutide. [64637] Ziprasidone: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. [28915] [30575]
      Revision Date: 03/28/2024, 01:48:00 AM

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      Monitoring Parameters

      • blood glucose
      • glycosylated hemoglobin A1c (HbA1c)
      • heart rate
      • weight

      US Drug Names

      • OZEMPIC
      • Rybelsus
      • Wegovy
      ;