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Jan.25.2021View related content

Obesity in adults

Synopsis

Key Points

  • Obesity is an excess of body fat, which is estimated clinically by the relationship between height and weight (ie, BMI), taking into account age, ethnicity, fluid status, and muscularity (eg, including waist circumference or waist-hip ratio along with BMI)
  • Overweight and obesity are generally defined by the following BMI levels: overweight, 25 to 29.9 kg/m²; obesity, 30 kg/m² or more
  • Metabolic, biomechanical, and psychosocial consequences of obesity have significant health implications, including hypertension, diabetes, dyslipidemia, cancer, coronary artery disease, obstructive sleep apnea, and osteoarthritis
  • Work-up should include history, review of systems, physical examination, fasting lipid panel, and fasting levels of glucose, hemoglobin A1C, and liver enzymes to assess for weight-related comorbidities and complications, with additional investigations for evaluation of specific comorbidities as indicated by clinical findings
  • Assess for and treat cardiovascular risk factors, obesity-related conditions, and contributing factors or secondary causes
  • First line therapy for all patients with BMI of 25 kg/m² or higher is lifestyle modification consisting of reduced-calorie diet in conjunction with physical activity and behavioral therapy to achieve weight loss; enrollment in a 6-month comprehensive weight loss program is recommended
  • Pharmacotherapy is indicated as an adjunct to lifestyle therapy for patients with BMI of 30 kg/m² or more, for those with BMI of 27 kg/m² or more plus obesity-related comorbidity, and for those in whom lifestyle modification alone fails to achieve weight loss goals; agents include phentermine, phentermine-topiramate extended-release, naltrexone-bupropion extended-release, liraglutide, and orlistat
  • On February 13, 2020, the FDA released a Drug Safety Communication indicating that it requested that the manufacturer of Belviq and Belviq XR (lorcaserin) voluntarily withdraw this weight loss drug from the US market because a safety clinical trial showed an increased occurrence of cancer. The drug manufacturer submitted a request to voluntarily withdraw the drug r1
  • Consider bariatric surgery for patients with BMI of 40 kg/m² or more, for those with BMI of 35 kg/m² or more plus obesity-related comorbidity, and for those in whom sufficient weight loss has not been achieved by other methods; it may be considered for patients with BMI less than 35 kg/m² with diabetes or metabolic syndrome
  • Obesity is typically a chronic condition, and it can be difficult for patients to maintain a healthy weight; usual pattern with lifestyle and pharmacologic intervention is maximal weight loss at 6 months followed by plateau and gradual regaining of weight over time

Urgent Action

  • Evaluate all obese patients for obesity-related comorbidities, and counsel them regarding their increased risk of cardiovascular disease

Pitfalls

  • BMI does not accurately distinguish fat mass from fat-free mass, thus very muscular people (or those who are muscular with large bones) may erroneously be classified as obese; include waist-hip ratio in their assessment
  • People of Asian descent may have delayed diagnosis of obesity due to failure to adjust BMI cutoff values downward for this population

Terminology

Clinical Clarification

  • Obesity is an excess of body fat; in clinical practice, this is estimated by the relationship between height and weight (ie, BMI), taking into account age, ethnicity, fluid status, and muscularityr2
  • Overweight and obesity are generally defined by the following BMI levels, which are associated with increased risk of adverse health effects r3
    • Overweight is defined as BMI of 25 to 29.9 kg/m² r3
    • Obesity is defined as BMI of 30 kg/m² or more r3
  • Metabolic, biomechanical, and psychosocial consequences of obesity have significant health implications r4

Classification

  • WHO international obesity classification based on BMI r5
    • Normal weight: BMI between 18.5 and 24.9 kg/m²
    • Overweight (preobese): BMI between 25 and 29.9 kg/m²
    • Obese: BMI of 30 kg/m² or more r6
      • Class 1 (mild): BMI between 30 and 34.9 kg/m² r6
      • Class 2 (moderate): BMI between 35 and 39.9 kg/m² r6
      • Class 3 (severe; morbid obesity): BMI of 40 kg/m² or more r6
    • BMI cutoff points have been defined differently for people of Asian descent based on usual body composition r2
      • Normal weight: BMI between 18.5 and 22.9 kg/m²
      • Overweight: BMI between 23 and 27.4 kg/m²
      • Obese: BMI of 27.5 kg/m² or more
      • People of Asian descent may have delayed diagnosis of obesity due to failure to adjust BMI cutoff values downward for this population
  • Phenotypic classification
    • Abdominal/central obesity (upper body obesity; "apple-shaped" body)
      • Regional and ethnic variations exist
        • Defined in some populations as waist circumference of 94 cm or more in men and 80 cm or more in women r2
        • In the United States and Canada, generally defined as waist circumference larger than 102 cm in men and larger than 88 cm in women r3
          • In people of Asian descent, defined as waist circumference of 85 cm or more in men and 80 cm or more in women (74 cm or more in women according to some references) r2
      • Waist-hip ratio of greater than 0.9 in men and greater than 0.85 in women also correlates with increased cardiovascular risk r7
    • Hip-thigh-gluteal obesity (lower body obesity; "pear-shaped" body)
      • Correlated with lower cardiovascular risk than central obesity; not protective and not equal in risk with healthy weight (as often described), but risk is lower compared with central obesity r8
  • Etiologic classification r9
    • Primary obesity
      • Most common form of obesity
      • Imbalance in energy intake and expenditure leads to accumulation of excess adipose tissue
      • Multifactorial causation with a polygenic basis; environmental factors result in weight gain in combination with other variables
    • Secondary obesity
      • Results from a disease or treatment (eg, hypothyroidism, growth hormone deficiency, certain medications)
    • Monogenic obesity
      • Affects a minority of patients
      • Alteration in single gene leads to early onset of severe obesity in childhood d1
      • Most common is mutation in MC4R (melanocortin 4 receptor); other forms include leptin deficiency, leptin receptor mutations, and deficiency of POMC (pro-opiomelanocortin) r10
      • May be associated with malformation syndromes (eg, Prader-Willi syndrome, Bardet-Biedl syndrome)

Diagnosis

Clinical Presentation

History

  • Obtain historical information about body weight
    • History of overweight or obesity in childhood and adulthood c1c2d1
    • Family history of obesity c3
    • Previous therapies for obesity and their effectiveness
    • History of eating disorders, including binge eating, anorexia, or bulimia c4c5c6
  • Obtain information about lifestyle habits that may be contributory
    • Current diet c7
    • Current physical activity level c8
    • Use of supplements or OTC diet aids c9
    • Sleep (amount and quality) c10
  • Obtain information about comorbidities and cardiovascular risk factors
    • Hypertension c11
    • Diabetes c12
    • Dyslipidemia c13
    • Sleep apnea c14
    • Coronary artery disease c15
    • Other atherosclerotic disease (eg, peripheral vascular disease, carotid artery disease) c16c17
    • Cigarette smoking c18
    • Family history of premature coronary artery disease c19
  • Identify medications that contribute to weight gain r11
    • Diabetes medications
    • Anticonvulsants c23
    • Tricyclic antidepressants c24
    • Antipsychotics c25
    • Oral contraceptives c26
    • Glucocorticoids c27
    • β-blockers c28
  • Ask about symptoms associated with secondary causes, complications, or comorbidities, as follows:
    • Snoring or disrupted sleep with daytime drowsiness may be sign of sleep apnea
    • Exercise intolerance or chest pain may be due to coronary artery disease/acute coronary syndrome c29c30
    • Abdominal pain may represent gallstones or gastroesophageal reflux c31c32
    • Headaches may be sign of systemic hypertension or idiopathic intracranial hypertension (pseudotumor cerebri) c33c34
    • Joint pain may be sign of osteoarthritis c35
    • Menstrual irregularity may be sign of polycystic ovary syndrome when accompanied by acne or hirsutism c36
    • Polyuria and polydipsia may be signs of type 2 diabetes c37c38
    • Fatigue with dry skin, poor appetite, and cold intolerance may be signs of hypothyroidism c39c40c41c42
    • Social isolation and lack of interest in activities may be signs of depression c43c44

Physical examination

  • Weight and height
    • Calculate BMI from height and weight: BMI = weight (kg)/height squared (m²) r3
      • Overweight: BMI between 25 and 29.9 kg/m² c45
      • Obese: BMI of 30 kg/m² or more c46
      • BMI thresholds are defined differently for people of Asian descent (overweight is BMI between 23 and 27.4 kg/m² and obese is BMI of 27.5 kg/m² or more) r2
  • Waist circumference
    • Measure waist circumference midway between the lowest palpable ribs and the iliac crestr12r7
      • In the United States and Canada, waist circumference larger than 102 cm in men and larger than 88 cm in women may indicate higher risk of obesity-related comorbidities than BMI alone r7c47c48
        • Among people of Asian descent, waist circumference of 85 cm or more in men and 80 cm or more in women (74 cm or more in women according to some references) should be considered abdominal obesity r2
    • Waist-hip ratio (ie, waist circumference over hip circumference) r7
      • At-risk results are a ratio greater than 0.9 in men and greater than 0.85 in women r7c49
      • BMI does not accurately distinguish fat mass from fat-free mass, thus very muscular people (or those who are muscular with large bones) may erroneously be classified as obese; include waist-hip ratio in their assessment
  • Vital signs
    • Blood pressure may be elevated c50
    • Ensure that appropriate cuff size is used for arm circumference
  • Skin findings
    • Intertrigo is common with large skin folds c51
    • Violaceous striae may be sign of Cushing syndrome c52
    • Acanthosis nigricans and skin tags may indicate insulin resistance c53c54
    • Severe acne with hirsutism suggests polycystic ovary syndrome c55c56
  • Signs associated with underlying causes or complications of obesity include:
    • Abnormal gait; hip, knee, or foot tenderness; or limited range of motion in hip or knee c57c58c59c60c61c62
    • Hepatomegaly or right upper quadrant tenderness c63c64
    • Goiter c65
    • Cushingoid appearance: round face and fat deposits on neck, upper back (buffalo hump), and abdomen c66c67
    • Dependent edema may be present in the ankles and feet c68

Causes and Risk Factors

Causes

  • Primary obesity is caused by complex relationships between genetics, nutrition, physical activity, and environmental factors c69c70c71c72
  • Obesity may be secondary to a variety of disease states, including: r11
    • Endocrine
      • Hypothyroidism c73
      • Growth hormone deficiency c74
      • Cushing syndrome c75
      • Pseudohypoparathyroidism c76
    • Psychological
      • Depression (when associated with overeating or bingeing) c77c78
      • Eating disorders c79
    • Neurologic
      • Hypothalamic dysfunction c80
      • Cranial irradiation c81
      • Brain tumors c82
      • Traumatic brain injury c83
    • Medications
      • Diabetes medications
      • Anticonvulsants c87
      • Tricyclic antidepressants c88
      • Antipsychotics c89
      • Oral contraceptives c90
      • Glucocorticoids c91
      • β-blockers c92
  • Obesity may accompany several genetic syndromes or single gene defects r11c93

Risk factors and/or associations

Age
  • Prevalence of obesity was just over 36% of US adults in 2011 to 2014 according to data from the National Health and Nutrition Examination Survey r13
    • Prevalence of obesity was higher among middle-aged adults (40.2%) and older adults (37%) than among younger adults (32.3%) r13c94c95c96
Sex
  • Prevalence of obesity was higher in women (38.3%) than in men (34.3%) in 2011 to 2014 according to data from the National Health and Nutrition Examination Survey r13c97c98
Genetics r9
  • Monogenic obesity
    • Mutation of MC4R (melanocortin 4 receptor) is associated with severe early-onset obesity, tall stature, and hyperphagia; it is the most common monogenic risk factorr10c99c100c101
    • Leptin deficiency and leptin receptor mutations are associated with severe early-onset obesity and hypogonadotropic hypogonadism c102c103
    • Deficiency of POMC (pro-opiomelanocortin) is associated with severe early-onset obesity, low plasma cortisol level, and skin and hair abnormalities c104c105c106
    • Deficiency of PCSK1 (prohormone convertase 1) is associated with severe early-onset obesity and low insulin and cortisol levels c107c108c109
    • Abnormalities in genes associated with hypothalamic development (eg, SIM1, BDNF, NTRK2) have been associated with obesity in a small number of cases c110c111c112
  • Syndromic obesity
    • Several genetic syndromes are associated with obesity and neurodevelopmental abnormalities (typically identified in childhood) d1
      • Prader-Willi syndrome c113d2
      • Bardet-Biedl syndrome c114
      • Alström syndrome c115
      • Wolfram syndrome c116
      • Beckwith-Wiedemann syndrome c117d3
      • WAGRO syndrome c118
      • Carpenter syndrome c119
      • Cohen syndrome c120
      • Down syndrome c121d4
      • MEHMO syndrome c122
      • MOMO syndrome c123
      • Smith-Magenis syndrome c124
      • Wilson-Turner syndrome c125
      • Börjeson-Forssman-Lehmann syndrome c126
  • Primary obesity
    • Era of genome-wide association studies is confirming that polygenic factors are important in primary obesity and is identifying relevant loci, although much remains unknown r14c127
Ethnicity/race
  • In the United States, prevalence of obesity in adults in 2011 to 2014 was lowest among non-Hispanic Asian Americans (11.7%), followed by non-Hispanic White (34.5%), Hispanic (42.5%), and non-Hispanic Black (48.1%) adults, according to data from the National Health and Nutrition Examination Survey r13c128c129c130c131
Other risk factors/associations r15
  • Sedentary lifestyle c132
  • Fast-food consumption c133
  • Increased intake of sugar-sweetened beverages c134
  • Early life factors (eg, parental BMI, birth weight, breastfeeding versus formula feeding) may influence childhood obesity, which is associated with adult obesity c135c136c137c138d1

Diagnostic Procedures

Primary diagnostic tools

  • Measure height and weight and calculate BMI at least annually r2c139
    • Diagnose obesity in patients with a BMI of 30 kg/m² or more; those with a BMI between 25 and 29.9 kg/m² are considered overweight r4c140c141
  • Also measure waist circumference in patients who are overweight or obese who have BMI less than 35 kg/m²; this measurement helps quantify cardiometabolic disease risk r2c142
  • Include history, review of systems, and physical examination in initial work-up to assess for weight-related comorbidities and complications c143c144
  • Although not strictly required for diagnosis, obtain fasting lipid panel and fasting glucose, hemoglobin A1C, and liver enzyme levels to screen for dyslipidemia, diabetes or prediabetes, and nonalcoholic fatty liver disease r2c145c146c147c148c149
  • Additional investigations may be indicated for evaluation of specific comorbidities or complications, including: r2
    • Endocrine evaluation if specific endocrine causes of obesity are suspected
    • Glucose tolerance test if diabetes is suspected
    • Polysomnography if sleep apnea is suspected
    • Abdominal ultrasonography for nonalcoholic fatty liver disease or polycystic ovary syndrome

Other diagnostic tools

  • Bioelectrical impedance analysis, skinfold measurement, and DXA are alternative methods to measure adiposity c150c151c152
    • Not recommended for routine clinical use r2

Differential Diagnosis

Most common

  • Secondary obesity c153
    • Obesity may be accompanied by signs and symptoms of underlying disorder (eg, hypothyroidism, Cushing syndrome) or associated with medication use c154c155c156
    • Differentiate on basis of history, physical examination findings, and laboratory test results (eg, thyroid function tests, cortisol levels) as directed by clinical findings
  • Monogenic obesity c157
    • Characterized by severe early-onset obesity starting in childhood
    • Suspect in patients who have history of unexplained weight gain from infancy and were in 97th percentile or greater for weight by age 3 years
    • May be differentiated based on genetic test results; however, this does not alter management
  • Syndromic obesity c158
    • Obesity develops in childhood in the context of various neurodevelopmental syndromes including trisomy 21 (Down syndrome), Prader-Willi syndrome, and Bardet-Biedl syndrome
    • Differentiate on basis of known diagnosis of specific syndrome or history and physical examination demonstrating characteristic dysmorphic and neurodevelopmental features thereof

Treatment

Goals

  • Reduce weight and maintain it within recommended range
  • Prevent or reverse obesity-related complications

Disposition

Admission criteria

  • Hospital admission is required for patients undergoing bariatric surgical procedure

Recommendations for specialist referral

  • All patients may benefit from consultation with an endocrinologist who has special expertise in treating obesity or an obesity medicine specialist
  • Referral to an endocrinologist is indicated if a hormonal cause of obesity is suspected
  • Referral to appropriate specialist (eg, orthopedic surgeon, psychologist) is indicated based on complications and suspected causes
  • Referral to a bariatric surgeon is recommended for patients with BMI higher than 40 kg/m², for those with BMI higher than 35 kg/m² plus comorbidity, and for those in whom lifestyle and medical management have failed to reduce weight

Treatment Options

Evaluate all obese patients for obesity-related comorbidities, and counsel them regarding their increased risk of cardiovascular disease

First line therapy for all patients with BMI of 25 kg/m² or higher is lifestyle modification consisting of reduced-calorie diet in conjunction with physical activity and behavioral therapy to achieve weight loss r2

  • Assess for and treat cardiovascular risk factors and obesity-related conditions r4
  • Treat contributing factors or secondary causes r11
  • Minimize use of medications that cause weight gain (eg, atypical antipsychotics, antidepressants, glucocorticoids, anticonvulsants, antihistamines, anticholinergics) r11

Pharmacotherapy is indicated as an adjunct to lifestyle therapy for patients with BMI of 30 kg/m² or more, for those with BMI of 27 kg/m² or more plus obesity-related comorbidityr6, and for those in whom lifestyle modification alone fails to achieve weight loss goals r4

  • Pharmacotherapy works by reinforcing behavioral strategies for weight loss; weight loss will be minimal without concurrent lifestyle change r11
  • Agents act by various mechanisms: influencing appetite and satiety (eg, phentermine, phentermine-topiramate extended-release, naltrexone-bupropion extended-release, liraglutide, diethylpropion), reducing dietary fat absorption (orlistat), or preventing reabsorption of glucose (eg, glucagonlike peptide 1 receptor agonists, sodium-glucose cotransporter 2 antagonists; used in diabetes therapy) r11
    • Endocrine Society guideliner11 provides useful table summarizing pharmacotherapy options
  • On February 13, 2020, the FDA released a Drug Safety Communication indicating that it requested that the manufacturer of Belviq and Belviq XR (lorcaserin) voluntarily withdraw this weight loss drug from the US market because a safety clinical trial showed an increased occurrence of cancer. The drug manufacturer submitted a request to voluntarily withdraw the drug r1
  • Dose titration is based on efficacy and tolerability to the recommended maximum approved dose
  • If regimen is ineffective (ie, weight loss less than 4%-5% of body weight at 3-4 months) or if there are safety/tolerability issues at any time, discontinue and consider alternative medications or referral to a bariatric specialist r11
  • No approved weight loss medication promotes long-term weight loss; weight will gradually rise again when the medication is stopped unless dietary restriction or activity level is intensified r11
    • Continue long-term if effective (ie, weight loss of 4%‐5% of body weight or more at 3-4 months) and safe/tolerable r11
      • Phentermine is not approved for long-term use; consider continuing only with guidance from state medical boards and local laws r11

Consider bariatric surgery for patients with BMI of 40 kg/m² or more, for those with BMI of 35 kg/m² or more plus any obesity-related comorbidityr6, or when sufficient weight loss has not been achieved by other methods r4

  • For patients with BMI lower than 35 kg/m², there is insufficient evidencer4 to recommend bariatric surgery, but it may be offered to patients with diabetes or metabolic syndromer16r17
  • Compared to nonsurgical management of obesity, bariatric surgery is associated with increased weight loss and significant improvement in obesity-associated comorbidities, regardless of type of surgical procedure r18
  • Common bariatric surgical procedures include Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, vertical sleeve gastrectomy, and biliopancreatic diversion and duodenal switch; they may be performed by laparoscopic approach or (rarely) open approach
  • Some surgical procedures produce greater weight loss and greater improvements in comorbidities, with the most effective being Roux-en-Y gastric bypass and gastric sleeve procedure r18

Drug therapy r11

  • Sympathomimetic amine anorectic with or without antiepileptic
    • Diethylpropion c159
      • Approved for short-term use (3 months) only
      • Immediate-release preparation c160
        • Diethylpropion Hydrochloride Oral tablet; Adults: 25 mg PO 3 times per day, 1 hour before meals. A 25 mg tablet may also be administered in the mid-evening if desired to overcome nighttime hunger. Use as monotherapy; for short-term use only.
      • Extended-release preparation
        • Diethylpropion Hydrochloride Oral tablet, extended-release; Adults: 75 mg PO once daily in mid-morning. Use as monotherapy; for short-term use only.
    • Phentermine r11c161c162
      • Approved for short-term use (3 months) only c163
      • Once daily dosing (phentermine hydrochloride 15 mg or more per oral capsule or tablet).
        • Phentermine Hydrochloride Oral tablet; Adults: 15 to 37.5 mg PO once daily every morning before breakfast or 1 to 2 hours after breakfast. Some tablets with a score may be divided, with 18.75 mg (half-tablet) given in the morning and the other half-tablet later in the day (but not in late evening), if needed. For some patients 18.75 mg PO once daily is sufficient. Geriatric patients may require lower dosage. Use as monotherapy; for short-term use only.
        • Phentermine Hydrochloride Oral tablet; Adolescents 17 years: 15 to 37.5 mg PO once daily every morning before breakfast or 1 to 2 hours after breakfast. Some tablets with a score may be divided, with 18.75 mg (half-tablet) given in the morning and the other half-tablet later in the day (but not in late evening), if needed. For some patients 18.75 mg PO once daily is sufficient. Use as monotherapy; for short-term use only.
      • 3 times daily dosing (phentermine hydrochloride 8 mg tablet). c164
        • Phentermine Hydrochloride Oral tablet; Adults: 8 mg PO 3 times per day, 30 minutes before meals. A dose of 4 mg PO 3 times per day may be used for patients not requiring the full dose. Geriatric patients should be initiated at the low end of the dosing range. Use as monotherapy; for short-term use only.
    • Topiramate-phentermine r11c165
      • Approved for weight loss and maintenance of weight loss c166
      • Phentermine Hydrochloride, Topiramate Oral capsule, extended-release; Adults: Initially, 3.75 mg/23 mg (phentermine/topiramate) PO once daily in the morning for 14 days. Target dose: 7.5 mg/46 mg PO once daily. Evaluate at 12 weeks; if patient has not lost 3% or more of baseline weight, discontinue therapy OR increase to 11.25 mg/69 mg PO once daily for 14 days, followed by 15 mg/92 mg PO once daily. Evaluate weight loss after 12 weeks; if patient has not lost at least 5% of baseline weight, discontinue. Use the 3.75 mg/23 mg and 11.25 mg/69 mg strengths for titration only. Guidelines recommend an initial dose of 3.75 mg/23 mg per day and a low maintenance dose of 7.5 mg/46 mg per day for obese patients with depression or anxiety. DISCONTINUATION: Reduce the 15 mg/92 mg dose gradually by dosing every other day for at least 1 week before stopping, to avoid precipitating a seizure.
  • Lipase inhibitor
    • Orlistat c167
      • Approved for weight loss and maintenance of weight loss
      • Available as OTC version or via prescription as a higher-strength capsule
      • Orlistat Oral capsule; Adults: 1 capsule (120 mg) PO 3 times per day with each main meal containing fat, taken during the meal or up to 1 hour after the meal. If a meal is occasionally missed or contains no fat, the dose of orlistat can be omitted. Because the absorption of fat-soluble vitamins A, D, E, K, and beta-carotene is reduced, supplement a daily multivitamin containing these vitamins at least 2 hours before or after orlistat.
  • Opioid antagonist–aminoketone antidepressant combination
    • Naltrexone-bupropion extended-release r11c168
      • Approved for weight loss and maintenance of weight loss
      • Naltrexone Hydrochloride, Bupropion Hydrochloride Oral tablet, extended-release; Adults: Titrate to target dose during the first 4 weeks of treatment, as follows: WEEK 1) 1 tablet (8 mg naltrexone/90 mg bupropion) PO once daily in the morning, no evening dose; WEEK 2) 1 tablet PO twice daily in the morning and evening; WEEK 3) 2 tablets PO in the morning, 1 tablet PO in the evening; WEEK 4 AND ONWARD) 2 tablets PO twice daily in the morning and evening. Max daily dose: 32 mg/360 mg per day (2 tablets PO twice daily). Evaluate response after 12 weeks at the maintenance dosage. If weight loss is less than 5% of baseline body weight, discontinue, as therapy is likely to be ineffective.
  • Glucagonlike peptide 1 receptor agonist
    • Liraglutide r11c169
      • Approved for weight loss and maintenance of weight loss
      • Liraglutide Solution for injection [Weight Management]; Adults: 0.6 mg subcutaneously once daily for 1 week to reduce risk for gastrointestinal (GI) symptoms; then, increase by 0.6 mg at weekly intervals until the target dose of 3 mg subcutaneously once daily is attained. Titrate more slowly if needed. The manufacturer recommends discontinuation if the 3 mg dose is not tolerated; efficacy has not been established at lower doses. Data are available for post-bariatric surgery use of liraglutide within a dose range of 1.8 to 3 mg/day. MISSED DOSES: If a dose is missed, resume the once daily regimen at the next scheduled dose. If more than 3 days have elapsed since the last dose, reinitiate at the 0.6 mg dose and re-titrate. PATIENT SELECTION: Liraglutide is indicated for patients with an initial body mass index (BMI) of 30 kg/m2 or more or in those with a BMI of 27 kg/m2 or more in the presence of at least 1 weight-related comorbid condition (e.g., hypertension, dyslipidemia, type 2 diabetes).

Nondrug and supportive care

Comprehensive lifestyle intervention r19

  • Initial treatment consists of diet, exercise, and behavioral modification r6c170c171c172
  • Dietary therapy
    • Prescribe diet to achieve reduced caloric intake: use 1 of the following approaches: r4
      • Prescribe caloric intake of 1200 to 1500 kcal/day for women and 1500 to 1800 kcal/day for men r4c173
      • Prescribe 500 to 750 kcal/day energy deficit r4
      • Prescribe an evidence-based diet that restricts certain food types to create energy deficit (eg, low-carbohydrate, low-fat, or high-fiber diet) c174c175c176
    • Various dietary approaches may be used to produce weight loss (eg, low-carbohydrate, low-fat, DASH, Mediterranean, high-protein, vegetarian) r2c177c178c179c180c181c182
      • Select according to patient preferences and health status
      • There is no evidence to suggest that any particular diet is superior to another across individuals; either the low-carbohydrate or low-fat approach can be recommended based on each patient's ability to tolerate and adhere to any particular diet r20
      • Any low-carbohydrate or low-fat diet can result in significant weight loss; low-carbohydrate diets produce slightly greater weight loss at 6 months than low-fat diets, but the difference in effect is minimal at 12 months r20
      • Weight loss on both low-carbohydrate and low-fat diets tends to slow or stop, with some regain of weight, between 6 and 12 months; regular exercise and participation in behavioral therapy tend to moderate this effect r20
    • In limited circumstances, a very-low-calorie diet (ie, fewer than 800 kcal/day) may be used under supervision in a medical setting with frequent follow-up by trained practitioners r4c183
  • Physical activity
    • Goal of 150 minutes or more per week of moderate-intensity exercise undertaken in 3 to 5 sessions throughout the week r2c184
    • Preferred program includes both aerobic and resistance training c185c186
    • Also encourage nonexercise and active leisure activity to reduce sedentary behavior r2c187
    • Increased duration and/or intensity of exercise may provide additional benefit if patient can tolerate it
  • Behavioral therapies to aid adherence to lower-calorie diet and increased physical activity consist of:
    • Setting goals: set a weight loss goal of 10% body weight loss in 6 months; an intermediate goal of 3% to 5% weight loss in 3 months may be helpful c188
    • Self-monitoring: record daily food and exercise and measure weight at regular intervals (eg, weekly) c189c190c191c192
    • Reducing stress, controlling stimulus, and using problem-solving strategies c193c194c195
    • Participate in a comprehensive lifestyle program for 6 months or more, as follows: r4
      • On-site, high-intensity group or individual comprehensive weight loss programs led by a trained interventionist (14 encounters or more per 6-month period) r4c196c197
      • Electronically or telephonically delivered programs with personal feedback from a trained interventionist c198c199c200c201c202c203c204c205c206c207c208c209c210c211
      • Commercial programs can be prescribed if evidence of safety and efficacy is reliable c212c213
    • Long-term (1 year or longer) participation in a comprehensive weight maintenance program for patients who achieve short-term weight loss goals
Procedures
Bariatric surgery c214c215c216c217
General explanation r21
  • Comprises a set of surgical procedures performed in obese patients to achieve and sustain substantial weight loss
  • Most common bariatric procedures include Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, vertical sleeve gastrectomy, and biliopancreatic diversion and duodenal switch c218c219c220c221
  • Type of procedure and approach depend on goals of therapy, patient factors (eg, age, severity of obesity, complications, comorbidities, behavioral and psychosocial factors, personal preferences), and local surgical expertise r4r16
  • Most bariatric surgical procedures are performed laparoscopically because they have lower early postoperative mortality and morbidity.r16 Open surgery is only rarely necessary
Indication r16
  • BMI of 40 kg/m² or more and no preexisting medical problems or excessive risk of complications
  • BMI of 35 to 39.9 kg/m² and any obesity-related complication
  • BMI of 30 to 34.9 kg/m² plus diabetes or metabolic syndrome is a possible indication; benefit in this population is not well established
Contraindications r22
  • Absolute
    • Diseases associated with poor long-term life expectancy
    • Poor myocardial reserve
    • Significant chronic obstructive pulmonary disease or respiratory dysfunction
    • Uncontrolled or untreated major depression or other psychiatric illnesses
    • Active substance misuse
    • Severe portal hypertension
    • Pregnancy or breastfeeding
  • Relative
    • History of nonadherence to medical care
    • Borderline personality disorder or bipolar disease
    • Moderate portal hypertension
Complications
  • Perioperative mortality rates are low;r18r17 1 large study found 0.3% mortality within 30 daysr22 after surgery
  • Depending on type of surgery, rates of severe adverse events range from 0% to 37%; rates of reoperation range from 2% to 13% r18
  • Complications may occur with all bariatric procedures
    • Anastomotic stricture
    • Gastrointestinal leak
    • Dumping syndrome
    • Small-bowel obstruction/internal hernia
    • Nutritional deficiencies owing to malabsorption
    • Thromboembolism
    • Gastric ulcer
    • Gallstones
    • Nephrolithiasis
    • Bone loss
  • Biliopancreatic diversion procedure is associated with high perioperative complication rate r18
    • Additional complications of hypoalbuminemia, fat malabsorption, and liver dysfunction
Interpretation of results
  • Benefits include weight loss, diabetes remission, cardiovascular risk reduction, and reduced mortality r16

Comorbidities

  • Evaluate all obese patients for obesity-related comorbidities and counsel them regarding their increased risk for cardiovascular disease
  • Cardiovascular disease c222
    • Obesity management considerations: r2
      • Orlistat is preferred by the American Association of Clinical Endocrinologists and American College of Endocrinology
      • Liraglutide, phentermine-topiramate extended-release, and naltrexone-bupropion extended-release can be used with caution and careful monitoring of heart rate and blood pressure
  • Hypertension r2c223d5
    • Obesity management considerations:
      • Avoid sympathomimetic pharmacotherapy for obesity (eg, phentermine) unless hypertension is well controlled
      • Orlistat and phentermine-topiramate extended-release are preferred weight loss medications according to the American Association of Clinical Endocrinologists and American College of Endocrinology
      • Avoid naltrexone-bupropion extended-release because it will not produce blood pressure lowering; it is contraindicated in uncontrolled hypertension
    • Use ACE inhibitors or angiotensin receptor blockers as first line drugs for blood pressure control
  • Diabetes c224d6
    • Select a regimen for diabetes management to include drugs that have favorable effects on body weight where possible;r23metformin is the first line agent for diabetes and obesityr11
      • Diabetes medication classes associated with weight gain include sulfonylureas, meglitinides, thiazolidinediones, and insulin
      • Diabetes medication classes that promote modest weight loss are metformin, glucagonlike peptide 1 receptor agonists, sodium-glucose cotransporter 2 inhibitors, and amylin mimetics
      • Diabetes medication classes that are weight neutral include dipeptidyl-peptidase IV inhibitors
  • Depression c225d7
    • Obesity management considerations: r2
      • Orlistat, liraglutide, and low doses of phentermine-topiramate extended-release are preferred weight loss medications
      • According to the American Association of Clinical Endocrinologists and American College of Endocrinology, naltrexone-bupropion extended-release can be used with caution
      • Consider potential for weight gain associated with antidepressants

Special populations

  • People of Asian ethnicity
    • BMI cutoff points have been defined differently for people of Asian descent based on usual body composition r2
      • Normal weight: BMI between 18.5 and 22.9 kg/m²
      • Overweight: BMI between 23 and 27.4 kg/m²
      • Obese: BMI of 27.5 kg/m² or more
  • Women of childbearing age desiring hormonal contraception (without other contraindications)
    • No evidence that combination hormonal contraception (estrogen plus a progestin) is associated with weight change r24
    • Limited evidence that progestin-only contraceptives are associated with weight gain (mean weight gain is less than 2 kg) r25
    • If BMI is 27 kg/m² or higher with comorbidities or 30 kg/m² or higher, recommend oral contraceptives over injectable progestin-only medications
    • There may be a higher incidence of contraceptive failure in patients with BMI higher than 27 kg/m², but evidence is conflicting
  • Pregnant patients
    • Pharmacologic and surgical therapies for obesity are contraindicated during pregnancy r23r26
    • Advise patients to wait a minimum of 12 to 18 months after bariatric surgery before attempting pregnancy r26

Monitoring

  • Frequency of visits depends on intensity and stage of treatment
  • Lifestyle interventions have best weight loss outcomes with frequent follow-up visits (14-16 over a 6-month period) and at least weekly self-monitoring (weighing)r4r4r11c226c227
  • Assess efficacy and adverse effects of pharmacotherapy at least monthly for the first 3 months, then at least every 3 months thereafter r11c228c229
  • Long-term follow-up consists of measuring weight and calculating BMI at least annually r4c230

Complications and Prognosis

Complications

  • Obesity-related conditions affect almost every system and include: r2
    • Hypertension c231
    • Cardiovascular disease c232
    • Type 2 diabetes/prediabetes r6c233c234
    • Metabolic syndrome c235
    • Dyslipidemia c236
    • Nonalcoholic fatty liver disease r6
      • Nonalcoholic steatohepatitis r16c237
    • Osteoarthritis c238
    • Obstructive sleep apnea c239
    • Obesity-hypoventilation syndrome r16c240
    • Worsening asthma/obstructive airway disease c241c242
    • Polycystic ovary syndrome c243
    • Depression c244
    • Gastroesophageal reflux disease c245
    • Female infertility c246
    • Male hypogonadism c247
    • Urinary stress incontinence c248
    • Gallbladder disease r6r27c249
    • Pseudotumor cerebri r16c250
    • Venous stasis r16c251
    • Gout r6c252
  • Obesity is also associated with an increased risk of certain types of cancer r27

Prognosis

  • Obesity is typically a chronic condition, and it can be difficult for patients to maintain a healthy weight; usual pattern with lifestyle and pharmacologic intervention is maximal weight loss at 6 months followed by plateau and gradual regaining of weight over time; may take longer for weight loss to plateau after bariatric surgery r4
  • Overweight and obesity are associated with increased risk of cardiovascular disease, type 2 diabetes, and all-cause mortality; risk increases in proportion to increase in BMI r4
  • Weight loss has been shown to reduce risk of cardiovascular disease and diabetes and may decrease mortality

Screening and Prevention

Screening

At-risk populations

  • Universal screening is recommended r4
    • All adults in the United States should be screened for obesity at least annually during regular medical office visits c259

Screening tests

  • Measure weight and height; calculate BMI r4c260
  • Assess diet, physical activity, and sedentary behaviors r4c261c262

Prevention

  • Promote healthy eating, regular physical activity, and avoidance of weight gain in patients with healthy weight and in those who are overweight but have no other risk factors for cardiovascular disease or obesity-related conditions r4c263c264c265
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