Obesity in Adults

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 ^c4c5c6c7
• Obtain information about lifestyle habits that may be contributory ^c8
  • Current diet
  • Current physical activity level
  • 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 ^r10
  • Anticonvulsants ^c20
  • Antipsychotics ^c21
  • β-blockers ^c22
  • Diabetes medications
    • Insulin ^c23
    • Sulfonylureas ^c24
    • Thiazolidinediones ^c25
  • Glucocorticoids ^c26
  • Oral contraceptives ^c27
  • Tricyclic antidepressants ^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 ^c31
  • Headaches may be sign of systemic hypertension or idiopathic intracranial hypertension (pseudotumor cerebri) ^c32
  • Joint pain may be sign of osteoarthritis ^c33
  • Menstrual irregularity may be sign of polycystic ovary syndrome when accompanied by acne or hirsutism ^c34
  • Polyuria and polydipsia may be signs of type 2 diabetes ^c35c36
  • Fatigue with dry skin, poor appetite, and cold intolerance may be signs of hypothyroidism ^c37c38c39c40
  • Social isolation and lack of interest in activities may be signs of depression ^c41c42

Physical examination

• Weight and height
  • Calculate BMI from height and weight: BMI = weight (kg)/height squared (m²) ^r2
    • Overweight: BMI between 25 and 29.9 kg/m² ^c43
    • Obese: BMI of 30 kg/m² or more ^c44
    • 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) ^r1
• Waist circumference
  • Measure waist circumference midway between the lowest palpable ribs and the iliac crest^r6r11
    • In the United States and Canada, waist circumference larger than 102 cm in males and larger than 88 cm in females may indicate higher risk of obesity-related comorbidities than BMI alone ^r6c45c46
      • Among people of Asian descent, waist circumference of 85 cm or more in males and 80 cm or more in females (74 cm or more in females according to some references) should be considered abdominal obesity ^r1
  • Waist-hip ratio (ie, waist circumference over hip circumference) ^r6
    • At-risk results are a ratio greater than 0.9 in males and greater than 0.85 in females ^r6c47
    • 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 ^c48
  • Ensure that appropriate cuff size is used for arm circumference
• Skin findings
  • Intertrigo is common with large skin folds ^c49
  • Violaceous striae may be sign of Cushing syndrome ^c50
  • Acanthosis nigricans and skin tags may indicate insulin resistance ^c51c52
  • Severe acne with hirsutism suggests polycystic ovary syndrome ^c53c54
• 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 ^{c55c56c57c58c59c60}
  • Hepatomegaly or right upper quadrant tenderness ^c61c62
  • Goiter ^c63
  • Cushingoid appearance: round face and fat deposits on neck, upper back (buffalo hump), and abdomen ^c64c65
  • Dependent edema may be present in the ankles and feet ^c66

Causes

• Primary obesity is caused by complex relationships between genetics, nutrition, physical activity, and environmental factors ^c67c68c69c70
• Obesity may be secondary to a variety of disease states, including: ^r10
  • Endocrine
    • Hypothyroidism ^c71
    • Growth hormone deficiency ^c72
    • Cushing syndrome ^c73
    • Pseudohypoparathyroidism ^c74
  • Psychological
    • Depression (when associated with overeating or bingeing) ^c75
    • Eating disorders ^c76
  • Neurologic
    • Hypothalamic dysfunction ^c77
    • Cranial irradiation ^c78
    • Brain tumors ^c79
    • Traumatic brain injury ^c80
  • Medications that may contribute to excess adiposity include:
    • Anticonvulsants ^c81
    • Antipsychotics ^c82
    • β-blockers ^c83
    • Diabetes medications
      • Insulin ^c84
      • Sulfonylureas ^c85
      • Thiazolidinediones ^c86
    • Glucocorticoids ^c87
    • Oral contraceptives ^c88
    • Tricyclic antidepressants ^c89
• Obesity may accompany several genetic syndromes or single gene defects ^r10c90

Risk factors and/or associations

Primary diagnostic tools

• Measure height and weight and calculate BMI at least annually ^r1c130
  • 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 ^r3c131c132
• 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 ^r1c133
• Include history, review of systems, and physical examination in initial workup to assess for weight-related comorbidities and complications ^c134c135
• 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 ^{r1c136c137c138c139c140}
• Additional investigations may be indicated for evaluation of specific comorbidities or complications, including: ^r1
  • Endocrine evaluation if specific endocrine causes of obesity are suspected
  • Glucose tolerance test if diabetes is suspected ^c141
  • Polysomnography if sleep apnea is suspected ^c142
  • Abdominal ultrasonography for nonalcoholic fatty liver disease or polycystic ovary syndrome ^c143

Other diagnostic tools

• Bioelectrical impedance analysis, skinfold measurement, and DXA are alternative methods to measure adiposity ^c144c145c146
  • Not recommended for routine clinical use ^r1

Most common

• Secondary obesity ^c147
  • Obesity may be accompanied by signs and symptoms of underlying disorder (eg, hypothyroidism, Cushing syndrome) or associated with medication use ^c148c149c150
  • 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 ^c151
  • 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 ^c152
  • 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

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 an 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

Drug therapy ^r10

• Sympathomimetic amine anorectic with or without antiepileptic
  • Diethylpropion ^c153
    • For short-term use (3 months) only ^r10
    • Immediate-release ^c154
      • Diethylpropion Hydrochloride Oral tablet; Adults: 25 mg PO 3 times daily.
    • Extended-release
      • Diethylpropion Hydrochloride Oral tablet, extended-release; Adults: 75 mg PO once daily.
  • Phentermine ^r10c155
    • For short-term use (3 months) only ^r10c156
    • 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 or 18.75 mg PO twice daily.
    • 3 times daily dosing (phentermine hydrochloride 8-mg tablet)
      • Phentermine Hydrochloride Oral tablet; Adults: 4 or 8 mg PO 3 times daily. Usual dose: 8 mg PO 3 times daily.
  • Topiramate-phentermine ^r10c157
    • Approved for weight loss and maintenance of weight loss
    • Phentermine Hydrochloride, Topiramate Oral capsule, extended-release; Adults: 3.75 mg phentermine/23 mg topiramate PO once daily for 14 days, then increase the dose to 7.5 mg phentermine/46 mg topiramate PO once daily. If weight loss is not at least 3% of baseline weight after 12 weeks, increase the dose to 11.25 mg phentermine/69 mg topiramate PO once daily for 14 days, and then 15 mg phentermine/92 mg topiramate PO once daily. If weight loss is not at least 5% of baseline weight after another 12 weeks, discontinue therapy.
• Lipase inhibitor
  • Orlistat ^c158
    • Approved for weight loss and maintenance of weight loss
    • Prescription strength
      • Orlistat Oral capsule; Adults: 120 mg PO 3 times daily with each main meal containing fat. May omit dose if a meal is occasionally missed or contains no fat.
    • OTC strength
      • Orlistat Oral capsule; Adults: 60 mg PO 3 times daily with each main meal containing fat. May omit dose if a meal is occasionally missed or contains no fat. Max: 180 mg/day.
• Opioid antagonist–aminoketone antidepressant combination
  • Naltrexone-bupropion ^r10c159
    • Approved for weight loss and maintenance of weight loss
    • Naltrexone Hydrochloride, Bupropion Hydrochloride Oral tablet, extended-release; Adults: 8 mg naltrexone/90 mg bupropion PO once daily for week 1, then 8 mg naltrexone/90 mg bupropion PO twice daily for 1 week, then 16 mg naltrexone/180 mg bupropion PO in the morning and 8 mg naltrexone/90 mg bupropion PO in the evening for 1 week, and then 16 mg naltrexone/180 mg bupropion PO twice daily. If weight loss is not lost at least 5% of baseline weight after 12 weeks, discontinue therapy. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
• Glucagonlike peptide 1 receptor agonist
  • Liraglutide ^r10c160
    • 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, initially. Then increase the dose by 0.6 mg/week to 3 mg subcutaneously once daily. Consider delaying dose escalation for 1 additional week if a dose increase is not tolerated. If the 3 mg dose is not tolerated or if weight loss is not at least 4% of baseline weight after 16 weeks, discontinue therapy.
  • Semaglutide ^r22r23
    • Approved for weight loss and maintenance of weight loss
    • Semaglutide Solution for injection [Weight Management]; 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, and then 2.4 mg subcutaneously once weekly. Consider delaying dose escalation for 4 weeks if a dose increase is not tolerated. May temporarily decrease dose to 1.7 mg subcutaneously once weekly for a maximum of 4 weeks if the 2.4 mg dose is not tolerated; resume 2.4 mg subcutaneously once weekly after 4 weeks. Discontinue use if the 2.4 mg dose is not tolerated.
• Melanocortin 4 (MC4) receptor agonist
  • Setmelanotide ^r24
    • For obesity due to POMC (pro-opiomelanocortin), PCSK1 (proprotein convertase subtilisin/kexin type 1), or LEPR (leptin receptor) deficiency
      • Setmelanotide Solution for injection; Adults: 2 mg subcutaneously once daily for 2 weeks, initially; reduce dose to 1 mg subcutaneously once daily if the 2 mg dose is not tolerated, and then increase the dose to 2 mg subcutaneously once daily if the 1 mg dose is tolerated for at least 1 week. Increase the dose to 3 mg subcutaneously once daily if the 2 mg dose is tolerated for 2 weeks; reduce the dose to 2 mg subcutaneously once daily if the 3 mg dose is not tolerated. If weight loss is not at least 5% of baseline body weight after 12 to 16 weeks, discontinue therapy.
    • For obesity due to Bardet-Biedl syndrome
      • Setmelanotide Solution for injection; Adults: 2 mg subcutaneously once daily for 2 weeks, initially; reduce dose to 1 mg subcutaneously once daily if the 2 mg dose is not tolerated, and then increase the dose to 2 mg subcutaneously once daily if the 1 mg dose is tolerated for at least 1 week. Increase the dose to 3 mg subcutaneously once daily if the 2 mg dose is tolerated for 2 weeks; reduce the dose to 2 mg subcutaneously once daily if the 3 mg dose is not tolerated. If weight loss is not at least 5% of baseline body weight after 1 year, discontinue therapy.

Nondrug and supportive care

Comprehensive lifestyle intervention ^r25

• Initial treatment consists of diet, exercise, and behavioral modification ^{r5c161c162c163}
• Dietary therapy ^c164
  • Prescribe diet to achieve reduced caloric intake: use 1 of the following approaches: ^r3
    • Prescribe caloric intake of 1200 to 1500 kcal/day for females and 1500 to 1800 kcal/day for males ^r3c165
    • Prescribe 500 to 750 kcal/day energy deficit ^r3
    • Prescribe an evidence-based diet that restricts certain food types to create energy deficit (eg, low-carbohydrate, low-fat, or high-fiber diet) ^c166c167c168
  • Various dietary approaches may be used to produce weight loss (eg, low-carbohydrate, low-fat, DASH, Mediterranean, high-protein, vegetarian) ^{r1c169c170c171c172c173c174}
    • 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 ^r26
    • 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 ^r26
    • 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 ^r26
  • 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 ^r3c175
• Physical activity
  • Goal of 150 minutes or more per week of moderate-intensity exercise undertaken in 3 to 5 sessions throughout the week ^r1c176
  • Preferred program includes both aerobic and resistance training ^c177c178
  • Also encourage nonexercise and active leisure activity to reduce sedentary behavior ^r1c179
  • 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 ^c180
  • Self-monitoring: record daily food and exercise and measure weight at regular intervals (eg, weekly) ^{c181c182c183c184}
  • Reducing stress, controlling stimulus, and using problem-solving strategies ^c185c186c187
  • Participate in a comprehensive lifestyle program for 6 months or more, as follows: ^r3
    • On-site, high-intensity group or individual comprehensive weight loss programs led by a trained interventionist (14 encounters or more per 6-month period) ^r3c188c189
    • Electronically or telephonically delivered programs with personal feedback from a trained interventionist ^c190c191
    • Commercial programs can be prescribed if evidence of safety and efficacy is reliable ^c192c193
  • Long-term (1 year or longer) participation in a comprehensive weight maintenance program for patients who achieve short-term weight loss goals

Comorbidities

• Evaluate all obese patients for obesity-related comorbidities and counsel them regarding their increased risk for cardiovascular disease
• Cardiovascular disease ^c199
  • Obesity management considerations ^r1
    • Orlistat is preferred by the American Association of Clinical Endocrinologists and American College of Endocrinology
    • Liraglutide, phentermine-topiramate, and naltrexone-bupropion can be used with caution and careful monitoring of heart rate and blood pressure
• Hypertension ^r1c200d5
  • Obesity management considerations
    • Avoid sympathomimetic pharmacotherapy for obesity (eg, phentermine) unless hypertension is well controlled
    • Orlistat and phentermine-topiramate are preferred weight loss medications according to the American Association of Clinical Endocrinologists and American College of Endocrinology
    • Avoid naltrexone-bupropion because it will lower blood pressure; it is contraindicated in uncontrolled hypertension
  • Use ACE inhibitors or angiotensin receptor blockers as first line drugs for blood pressure control
• Diabetes ^c201d6
  • Select drugs to control diabetes that have favorable effects on body weight where possible;^r18metformin is the first line agent for diabetes and obesity^r10
    • Diabetes medication classes associated with weight gain include sulfonylureas, meglitinides, thiazolidinediones, and insulin ^r18
    • Classes of diabetes medication that promote varying degrees of weight loss include metformin, glucagonlike peptide-1 receptor agonists, dual glucagonlike peptide 1/glucose–dependent insulinotropic polypeptide receptor agonist, α-glucosidase inhibitors, sodium-glucose-linked transporter-2 inhibitors, and amylin mimetics ^r18
    • Diabetes medication classes that are weight neutral include dipeptidyl-peptidase IV inhibitors ^r18
• Depression ^c202d7
  • Obesity management considerations ^r1
    • Orlistat, liraglutide, and low doses of phentermine-topiramate are preferred weight loss medications
    • According to the American Association of Clinical Endocrinologists and American College of Endocrinology, naltrexone-bupropion 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. These altered ranges have implications for indications for pharmacotherapy and bariatric surgery. ^r1
    • 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
• Pregnant patients
  • Pharmacologic and surgical therapies for obesity are contraindicated during pregnancy ^r29
  • Advise patients to wait a minimum of 12 to 18 months after bariatric surgery before attempting pregnancy ^r29
• Genetic forms of obesity
  • Patients with obesity due to Bardet-Biedl or to sequence variants in various genes [POMC (pro-opiomelanocortin), PCSK1 (proprotein convertase subtilisin/kexin type 1), and LEPR (leptin receptor)] are candidates for pharmacotherapy with setmelanotide ^r24
  • Setmelanotide is an MC4 (melanocortin 4) receptor agonist
    • Reestablishing MC4 receptor pathway activity reduces hunger and promotes weight loss by reducing caloric intake and increasing energy expenditure
    • In 1 randomized controlled trial, the mean percentage of weight loss after 1 year of use was 25.6% in those with POMC (pro-opiomelanocortin) deficiency and 12.5% in those with LEPR (leptin receptor) deficiency ^r30
    • In another randomized controlled trial, mean percentage of weight loss after 1 year of use was 9.1% in those with Bardet-Biedl ^r31
• Females of childbearing age desiring hormonal contraception (without other contraindications)
  • No evidence that combination hormonal contraception (estrogen plus a progestin) is associated with weight change ^r32
  • Limited evidence that progestin-only contraceptives are associated with weight gain (mean weight gain is less than 2 kg) ^r33
  • 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

At-risk populations

• Universal screening is recommended ^r3
  • All adults in the United States should be screened for obesity at least annually during regular medical office visits ^c236

Screening tests

• Measure weight and height; calculate BMI ^r3c237
• Assess diet, physical activity, and sedentary behaviors ^r3c238c239