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Obesity in Adults

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Apr.03.2023

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
  • Workup 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, naltrexone-bupropion, liraglutide, semaglutide, and orlistat
  • 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 also be considered for patients with BMI less than 35 kg/m² with type 2 diabetes or metabolic syndrome
  • Obesity is typically a chronic condition, and it can be difficult for patients to maintain a healthy weight; lifestyle and pharmacologic intervention typically yields a maximal weight loss at 6 months followed by plateau; if medications are not discontinued, gradual weight is usually regained 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 muscularityr1
  • Overweight and obesity are generally defined by the following BMI levels, which are associated with increased risk of adverse health effects: r2
    • Overweight is defined as BMI of 25 to 29.9 kg/m² r2
    • Obesity is defined as BMI of 30 kg/m² or more r2
  • Metabolic, biomechanical, and psychosocial consequences of obesity have significant health implications r3

Classification

  • WHO international obesity classification based on BMI r4
    • 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 r5
      • Class 1 (mild): BMI between 30 and 34.9 kg/m² r5
      • Class 2 (moderate): BMI between 35 and 39.9 kg/m² r5
      • Class 3 (severe; morbid obesity): BMI of 40 kg/m² or more r5
    • BMI cutoff points have been defined differently for people of Asian descent based on usual body composition 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
      • 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 males and 80 cm or more in females r1
        • In the United States and Canada, generally defined as waist circumference larger than 102 cm in males and larger than 88 cm in females r2
          • In people of Asian descent, defined as 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) r1
      • Waist-hip ratio of greater than 0.9 in males and greater than 0.85 in females also correlates with increased cardiovascular risk r6
    • 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 r7
  • Etiologic classification r8
    • 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) r9
      • 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 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 crestr6r11
      • 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 and Risk Factors

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

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 r12
    • Prevalence of obesity was higher among middle-aged adults (40.2%) and older adults (37%) than among younger adults (32.3%) r12c91c92c93
Sex
  • Prevalence of obesity was higher in females (38.3%) than in males (34.3%) in 2011 to 2014 according to data from the National Health and Nutrition Examination Survey r12c94c95
Genetics r8
  • 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 factorr9c96
    • Leptin deficiency and LEPR (leptin receptor) mutations are associated with severe early-onset obesity and hypogonadotropic hypogonadism c97c98
    • Deficiency of POMC (pro-opiomelanocortin) is associated with severe early-onset obesity, low plasma cortisol level, and skin and hair abnormalities c99
    • Deficiency of PCSK1 (prohormone convertase 1) is associated with severe early-onset obesity and low insulin and cortisol levels c100
    • Abnormalities in genes associated with hypothalamic development (eg, SIM1, BDNF, NTRK2) have been associated with obesity in a small number of cases c101c102c103
  • Syndromic obesity
    • Several genetic syndromes are associated with obesity and neurodevelopmental abnormalities (typically identified in childhood) d1
      • Prader-Willi syndrome c104d2
      • Bardet-Biedl syndrome c105
      • Alström syndrome c106
      • Wolfram syndrome c107
      • Beckwith-Wiedemann syndrome c108d3
      • WAGRO syndrome c109
      • Carpenter syndrome c110
      • Cohen syndrome c111
      • Down syndrome c112d4
      • MEHMO syndrome c113
      • MOMO syndrome c114
      • Smith-Magenis syndrome c115
      • Wilson-Turner syndrome c116
      • Börjeson-Forssman-Lehmann syndrome c117
  • 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 r13c118
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 r12c119c120c121c122
Other risk factors/associations r14
  • Sedentary lifestyle c123
  • Fast-food consumption c124
  • Increased intake of sugar-sweetened beverages c125
  • Early life factors (eg, parental BMI, birth weight, breastfeeding versus formula feeding) may influence childhood obesity, which is associated with adult obesity c126c127c128c129d1

Diagnostic Procedures

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

Differential Diagnosis

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

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 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

Treatment Options

Treatment options for adults with obesity include lifestyle modifications, pharmacotherapy, and bariatric surgery

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 r1

  • Counsel patients on and treat cardiovascular risk factors and obesity-related conditions r3
  • Treat contributing factors or secondary causes r10
  • Minimize use of medications that cause weight gain (eg, atypical antipsychotics, antidepressants, glucocorticoids, anticonvulsants, antihistamines, anticholinergics) r10

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,r5 and for those in whom lifestyle modification alone fails to achieve weight loss goals r3

  • Pharmacotherapy works by reinforcing behavioral strategies for weight loss; weight loss will be minimal without concurrent lifestyle change r10
  • Agents act by various mechanisms: influencing appetite and satiety (eg, diethylpropion, phentermine, phentermine-topiramate, naltrexone-bupropion, liraglutide, semaglutide, setmelanotide), reducing dietary fat absorption (orlistat), and/or preventing reabsorption of glucose (eg, glucagonlike peptide-1 receptor agonists, sodium-glucose-linked transporter-2 antagonists; used in diabetes therapy) r10
    • Selection of a particular medication is individualized, based upon medical comorbidities, contraindications, patient preferences, and insurance formularies r15r16
    • Endocrine Society guideliner10 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 r17
  • 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 r10
  • 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 r10
    • Continue long term if effective (ie, weight loss of 4%‐5% of body weight or more at 3-4 months) and safe/tolerable r10
      • Diethylpropion and phentermine are not approved for long-term use; consider continuing only with guidance from state medical boards and local laws r10

Consider bariatric surgery for patients with BMI of 40 kg/m² or more, for those with BMI of 30-35 kg/m² or more plus any obesity-related comorbidity,r5 or when sufficient weight loss has not been achieved by other methods r3r18

  • For patients with BMI lower than 35 kg/m², there is insufficient evidencer3 to recommend bariatric surgery, but it may be offered to patients with diabetes or metabolic syndromer19r20
  • 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 r21
  • 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 r21

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
Procedures
Bariatric surgery c194
General explanation r27
  • 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 c195c196c197c198
  • 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 r3r20
  • Most bariatric surgical procedures are performed laparoscopically because they have lower early postoperative mortality and morbidity.r20 Open surgery is only rarely necessary
Indication r20
  • Bariatric surgery is indicated for individuals who are unable to achieve and maintain sufficient weight loss (or improve comorbidities) using nonsurgical methods at the following BMI thresholds:
    • 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 type 2 diabetes or metabolic syndrome is a possible indication; benefit in this population is not well established
Contraindications r28
  • 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;r21r19 1 large study found 0.3% mortality within 30 daysr28 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% r21
  • 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 r21
    • Additional complications of hypoalbuminemia, fat malabsorption, and liver dysfunction
Interpretation of results
  • Benefits include weight loss, diabetes remission, cardiovascular risk reduction, and reduced mortality r20

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 obesityr10
      • 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

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)r3r3r10c203c204
  • Assess efficacy and adverse effects of pharmacotherapy at least monthly for the first 3 months, then at least every 3 months thereafter r10c205c206
  • Long-term follow-up consists of measuring weight and calculating BMI at least annually r3c207

Complications and Prognosis

Complications

  • Obesity-related conditions affect almost every system and include: r1
    • Hypertension c208
    • Cardiovascular disease c209
    • Type 2 diabetes/prediabetes r5c210c211
    • Metabolic syndrome c212
    • Dyslipidemia c213
    • Nonalcoholic fatty liver disease r5
      • Nonalcoholic steatohepatitis r20c214
    • Osteoarthritis c215
    • Obstructive sleep apnea c216
    • Obesity-hypoventilation syndrome r20c217
    • Worsening asthma/obstructive airway disease c218c219
    • Polycystic ovary syndrome c220
    • Depression c221
    • Gastroesophageal reflux disease c222
    • Female infertility c223
    • Male hypogonadism c224
    • Urinary stress incontinence c225
    • Gallbladder disease r5r34c226
    • Pseudotumor cerebri r20c227
    • Venous stasis r20c228
    • Gout r5c229
  • Obesity is also associated with an increased risk of certain types of cancer r34

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 r3
  • 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 r3
  • 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 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

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 r3c240c241c242
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