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Hyperglycemic hyperosmolar state r45
Hypoglycemia with neuroglycopenia r43
Uncontrolled diabetes r43
Comprehensive diabetes management encompasses several components, including therapeutic lifestyle changes, pharmacotherapy, glucose monitoring, diabetes education, and strategies to reduce cardiovascular risk factors
All patients should engage in lifestyle modifications directed at weight loss and increased physical activity r47r48
General guidance on pharmacologic therapy
Antihyperglycemic medications
Self-monitoring of blood glucose level r72
Bariatric surgery
Management of comorbidities
Drug class | Hemoglobin A1C–lowering effect | Hypoglycemia risk | Cardiovascular effects | Effect on body weight | Comments |
---|---|---|---|---|---|
GLP-1 receptor agonist | 1%-1.5% | Neutral | Liraglutide associated with reduction in major adverse cardiovascular events,* myocardial infarction, and reductions in cardiovascular and all-cause mortality; semaglutide associated with reduction in MACE (but not mortality)* | Loss | Contraindicated in patients with personal or family history of medullary thyroid carcinoma or MEN-2; renal function should be checked at baseline and periodically throughout therapy |
Combined insulin- GLP-1 receptor agonist | More than 1.5% | Moderate, due to insulin component | Allows less weight gain (or even promotes minor weight loss) that otherwise occurs with insulin | Same contraindications as with GLP-1 receptor agonist; renal function should be checked at baseline and periodically throughout therapy | |
Amylin Mimetic | 0.5% | Neutral alone, but increased risk of hypoglycemia when used with insulin (as indicated) | Slight loss; may limit weight gain that occurs with use of insulin | Indicated for use in conjunction with basal-bolus insulin regimens | |
Dual GIP and GLP-1 agonist | 1.8 - 2.07% | Neutral | SURPASS-CVOT trial underway to asses long-term cardiovascular outcomes | Loss | Same contraindications as with GLP-1 receptor agonists |
Type of insulin | Names | Time of action: onset, peak, and duration of effects | Comments |
---|---|---|---|
Basal | NPH | Onset: 2-4 hours Peak: 4-10 hours Duration: 10-18 hours | Variable action profile; can mix with rapid-acting insulins. NPH available as 100 unit/mL |
Basal analog | Glargine | Onset: 1.5 hours Peak: none Duration: 24 hours | Glargine available as 100 unit/mL as well as concentrated 300 unit/mL |
Detemir | Onset: 1-3 hours Peak: 6-8 hours Duration: 18-20 hours | Basal analog insulins provide similar hemoglobin A1C levels, better evening glucose levels, and less hypoglycemia compared to NPH. Determir available as 100 unit/mL | |
Degludec | Onset: 1 hour Peak: 12 hours Duration: more than 42 hours | Ultra-long-acting, once-daily basal analog with peakless activity. Degludec available as 100 unit/ml and 200 unit/mL | |
Bolus regular | Humulin R | Onset: 30 minutes Peak: 1.5-3.5 hours Duration: 5-7 hours | Longer duration compared to rapid- acting analogs makes regular insulin useful in gastroparesis. Available 100 unit/mL |
Bolus regular U-500 insulin | Humulin R U500 | Onset: 30 minutes Peak: 1.5-3.5 hours Duration: 5-7 hours | Use for insulin-resistant patients who need more than 200 total units per day, given 3 times per day. Available 500 unit/mL |
Bolus rapid-acting analog | Lispro, aspart, glulisine | Onset: 5-15 minutes Peak: 0.5-2 hours Duration: 3-5 hours | Rapid-acting analog insulin provides better control of postprandial glucose levels and less hypoglycemia compared with regular insulin; may be taken during or after meals. Lispro available 100 unit/mL and 200 unit/mL. Aspart and glulisine available as 100 unit/mL |
Premixed insulin (50/50, 70/30, 75/25, 80/20) | Humalog 75/25 or 50/50 mix, Novolog 70/30 mix, Novolin 70/30, Humulin 70/30 | Onset: 5-15 minutes Peak: 0.5-2 hours Duration: 3-5 hours | Titration of both basal and prandial must occur simultaneously; compared with use of basal insulin or basal bolus insulin regimens, there is an Increased rate of hypoglycemia with inferior achievement of glycemic goals |
Drug class | Hemoglobin A1C–lowering effect | Hypoglycemia risk | Micro- or macrovascular benefit | Weight change | Use in renal disease | Warnings | Comments |
---|---|---|---|---|---|---|---|
Biguanide | 1%-1.5% | Neutral | Reduction in cardiovascular events noted in UKPDS | Mostly neutral, but potential for slight loss | eGFR should be more than 45 mL/minute/1.73 m² at the time drug is started; thereafter, contraindicated if eGFR falls below 30 mL/minute/1.73 m² | Lactic acidosis risk | Vitamin B₁₂ deficiency can occur, and levels should be checked annually; drug should be discontinued on hospital admission, before administration of radiocontrast agents or in the setting of hypoxia or volume disturbance |
SGLT2 inhibitors | 0.5%-1% | Neutral | Empagliflozin has been shown to reduce cardiovascular and all-cause mortality and to slow progression of renal disease in nephropathy; canagliflozin has been shown to slow nephropathy | Loss | Requires renal dosing adjustments at chronic kidney disease stage 3 or greater; contraindicated if eGFR is less than 45 mL/minute/1.73 m² | Increased risk of bone fractures and increased risk of lower extremity amputations for canagliflozin; increased potential for DKA with all SGLT2 inhibitors | Reductions in blood pressure; risk for volume contraction; renal function should be checked at baseline and periodically throughout therapy |
Sulfonylureas | 1%-1.5% | Moderate to severe | Reduction in microvascular complications noted in UKPDS | Gain | Hypoglycemia risk increases with declining renal function; contraindicated in chronic kidney disease stage 4 | Glyburide not recommended with renal failure | Retrospective data suggest a possible cardiovascular risk with use of this class of drugs, as compared with metformin |
Meglitinides | 1% | Moderate | Gain | Hypoglycemia risk increases with declining renal function; may be used in chronic kidney disease stages 3-5 with dosing adjustments | Dosed multiple times per day at meals | ||
DPP4 inhibitors | 0.6%-0.8% | Neutral | Microvascular benefit of reducing albuminuria; potential risk for heart failure hospitalizations with saxagliptin | Neutral | Requires renal dosing adjustments, except linagliptin | Renal function should be checked at baseline and periodically throughout therapy; only linagliptin does not require adjustments for renal insufficiency | |
Thiazolidinediones | 1% | Neutral | Reduction in cardiovascular events noted in PROactive trial with pioglitazone, but drugs of this class increase incidence of heart failure | Gain | Risk of congestive heart failure (contraindicated in class III and IV heart failure), fracture risk, and possible risk of bladder cancer with pioglitazone | Possible benefit in nonalcoholic steatohepatitis; elevated risk of bone fractures; slight elevation in LDL cholesterol | |
α-glucosidase inhibitors | 0.5% | Neutral | Neutral | Nonsystemic absorption | |||
Dopamine-2 agonists | 0.5% | Neutral | Neutral |
Therapeutic lifestyle modifications r33r48c150
Diabetes self-management education and support r48c154
Blood glucose monitoring