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Feb.18.2020View 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- to 12-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
  • Note: On February 13, 2020, the FDA released a Drug Safety Communication indicating that it has 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 shows an increased occurrence of cancer. The drug manufacturer submitted a request to voluntarily withdraw the drugr1
  • Bariatric surgery should be considered 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

  • All patients with obesity should be evaluated for obesity-related comorbidities and counseled regarding their increased risk of cardiovascular disease

Pitfalls

  • BMI does not accurately distinguish fat mass from fat-free mass, so 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
      • Class 1 (mild): BMI between 30 and 34.9 kg/m²
      • Class 2 (moderate): BMI between 35 and 39.9 kg/m²
      • Class 3 (severe; "morbid obesity"): BMI of 40 kg/m² or more
    • 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 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 c1d1
    • Family history of obesity c2
    • Previous therapies for obesity and their effectiveness
    • History of eating disorders, including binge eating, anorexia, or bulimia c3c4c5
  • Obtain information about lifestyle habits that may be contributory
    • Current diet
    • Current physical activity level
    • Use of supplements or OTC diet aids
    • Sleep (amount and quality)
  • Obtain information about comorbidities and cardiovascular risk factors
    • Hypertension c6
    • Diabetes c7
    • Dyslipidemia c8
    • Sleep apnea c9
    • Coronary artery disease c10
    • Other atherosclerotic disease (eg, peripheral vascular disease, carotid artery disease) c11c12
    • Cigarette smoking c13
    • Family history of premature coronary artery disease c14
  • Identify medications that contribute to weight gain r10
    • Diabetes medications
    • Anticonvulsants c18
    • Tricyclic antidepressants c19
    • Antipsychotics c20
    • Oral contraceptives c21
    • Glucocorticoids c22
    • β-blockers c23
  • 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 c24c25c26
    • Exercise intolerance or chest pain may be due to coronary artery disease/acute coronary syndrome c27c28
    • Abdominal pain may represent gallstones or gastroesophageal reflux c29c30
    • Headaches may be sign of systemic hypertension or idiopathic intracranial hypertension (pseudotumor cerebri) c31c32
    • 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 c41

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 c42
      • Obese: BMI of 30 kg/m² or more c43
      • 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 crestr11r6
      • 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 r6c44c45
        • 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) r6
      • At-risk results are a ratio greater than 0.9 in men and greater than 0.85 in women r6
      • BMI does not accurately distinguish fat mass from fat-free mass, so 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 c46
    • Ensure that appropriate cuff size is used for arm circumference
  • Skin findings
    • Intertrigo is common with large skin folds c47
    • Violaceous striae may be sign of Cushing syndrome c48
    • Acanthosis nigricans and skin tags may indicate insulin resistance c49c50
    • Severe acne with hirsutism suggests polycystic ovary syndrome c51c52
  • 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 c53c54c55c56c57c58
    • Hepatomegaly or right upper quadrant tenderness c59c60
    • Goiter c61
    • Cushingoid appearance: round face and fat deposits on neck, upper back (buffalo hump), and abdomen c62c63
    • Dependent edema may be present in the ankles and feet c64

Causes and Risk Factors

Causes

  • Primary obesity is caused by complex relationships between genetics, nutrition, physical activity, and environmental factors c65c66c67c68
  • Obesity may be secondary to a variety of disease states, including: r10
    • Endocrine
      • Hypothyroidism c69
      • Growth hormone deficiency c70
      • Cushing syndrome c71
      • Pseudohypoparathyroidism c72
    • Psychological
      • Depression (when associated with overeating or bingeing) c73c74
      • Eating disorders c75
    • Neurologic
      • Hypothalamic dysfunction c76
      • Cranial irradiation c77
      • Brain tumors c78
      • Traumatic brain injury c79
    • Medications
      • Diabetes medications
      • Anticonvulsants c83
      • Tricyclic antidepressants c84
      • Antipsychotics c85
      • Oral contraceptives c86
      • Glucocorticoids c87
      • β-blockers c88
  • Obesity may accompany several genetic syndromes or single gene defects r10c89

Risk factors and/or associations

Age
  • Prevalence of obesity was just over 36% of US adults in 2011-2014 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%) r12c90c91c92
Sex
  • Prevalence of obesity was higher in women (38.3%) than in men (34.3%) in 2011-2014 according to data from the National Health and Nutrition Examination Survey r12c93c94
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 factorr9c95c96c97
    • Leptin deficiency and leptin receptor mutations are associated with severe early-onset obesity and hypogonadotropic hypogonadism c98c99
    • Deficiency of POMC (pro-opiomelanocortin) is associated with severe early-onset obesity, low plasma cortisol level, and skin and hair abnormalities c100c101c102
    • Deficiency of PCSK1 (prohormone convertase 1) is associated with severe early-onset obesity and low insulin and cortisol levels c103c104c105
    • Abnormalities in genes associated with hypothalamic development (eg, SIM1, BDNF, NTRK2) have been associated with obesity in a small number of cases c106c107c108
  • Syndromic obesity
    • Several genetic syndromes are associated with obesity and neurodevelopmental abnormalities (typically identified in childhood) d1
      • Prader-Willi syndrome c109d2
      • Bardet-Biedl syndrome c110
      • Alström syndrome c111
      • Wolfram syndrome c112
      • Beckwith-Wiedemann syndrome c113d3
      • WAGRO syndrome c114
      • Carpenter syndrome c115
      • Cohen syndrome c116
      • Down syndrome c117d4
      • MEHMO syndrome c118
      • MOMO syndrome c119
      • Smith-Magenis syndrome c120
      • Wilson-Turner syndrome c121
      • Börjeson-Forssman-Lehmann syndrome c122
  • 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 r13c123
Ethnicity/race
  • In the United States, prevalence of obesity in adults in 2011-2014 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 r12c124c125c126c127
Other risk factors/associations r14
  • Sedentary lifestyle c128
  • Fast-food consumption c129
  • Increased intake of sugar-sweetened beverages c130
  • Early life factors (eg, parental BMI, birth weight, breastfeeding versus formula feeding) may influence childhood obesity, which is associated with adult obesity c131c132c133c134d1

Diagnostic Procedures

Primary diagnostic tools

  • Measure height and weight and calculate BMI at least annually r2c135
    • 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 r4
  • Also measure waist circumference in patients who are overweight or obese with BMI less than 35 kg/m²; this measurement helps quantify cardiometabolic disease risk r2
  • Include history, review of systems, and physical examination in initial work-up to assess for weight-related comorbidities and complications
  • While 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 r2
  • 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

Laboratory

Other diagnostic tools

  • Bioelectrical impedance analysis, skinfold measurement, and DEXA are alternative methods to measure adiposity c136c137c138
    • Not recommended for routine clinical use r2

Differential Diagnosis

Most common

  • Secondary obesity c139
    • Obesity may be accompanied by signs and symptoms of underlying disorder (eg, hypothyroidism, Cushing syndrome) or associated with medication use
    • 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 c140
    • 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 on basis of genetic test results; however, this does not alter management
  • Syndromic obesity c141
    • 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

  • Weight reduction followed by maintenance within recommended range
  • Prevention or reversal of 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 a consultation with an endocrinologist with special expertise in the treatment of obesity or an obesity medicine specialist
  • Referral to an endocrinologist is indicated if a hormonal cause of obesity is suspected
  • Referral to appropriate specialist is indicated based on complications and suspected causes (eg, orthopedic surgeon, psychologist)
  • 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

All patients with obesity should be evaluated for obesity-related comorbidities and counseled 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 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, 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 r10
  • 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) r10
    • Endocrine Society guideliner10 provides useful table summarizing pharmacotherapy options
  • Note: On February 13, 2020, the FDA released a Drug Safety Communication indicating that it has 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 shows an increased occurrence of cancer. The drug manufacturer submitted a request to voluntarily withdraw the drugr1
  • Dose is titrated on basis of 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
      • Phentermine is not approved for long-term use; continuation should be considered only with guidance from state medical boards and local laws r10

Bariatric surgery should be considered for patients with BMI of 40 kg/m² or more, for those with BMI of 35 kg/m² or more plus any obesity-related comorbidity, 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 syndromer15
  • 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 r16
  • 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 r16

Drug therapy r10

  • Sympathomimetic amine anorectic with or without antiepileptic
    • Diethylpropion c142
      • Approved for short-term use (3 months) only
      • Immediate-release preparation
        • 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 r10c143c144
      • Approved for short-term use (3 months) only
      • Once daily dosing (phentermine hydrochloride 15 mg or more per oral capsule or tablet)
        • Phentermine Hydrochloride Oral tablet; Adults and Adolescents 17 years and older: 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; Adults and Adolescents 17 years and older: 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.
      • 3 times daily dosing (phentermine hydrochloride 8 mg tablet)
        • Phentermine Hydrochloride Oral tablet; Adults and Adolescents 17 years and older: 8 mg PO 3 times per day, 30 minutes before meals. Geriatric patients should be initiated at the low end of the dosing range. A dose of 4 mg PO 3 times per day may be used for patients not requiring the full dose. Use as monotherapy; for short-term use only.
    • Topiramate-phentermine r10c145
      • Approved for weight loss and maintenance of weight loss
      • 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 c146
      • 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 r10c147
      • 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 r10c148
      • 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 r17

  • Initial treatment consists of diet, exercise, and behavioral modification c149c150c151
  • Dietary therapy
    • Prescribe diet to achieve reduced caloric intake: use one of the following approaches: r4
      • Prescribe caloric intake of 1200 to 1500 kcal/day for women and 1500 to 1800 kcal/day for men r4c152
      • 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) c153c154c155
    • Various dietary approaches may be used to produce weight loss (eg, low-carbohydrate, low-fat, DASH, Mediterranean, high-protein, vegetarian) r2c156c157c158c159c160c161
      • 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 r18
      • 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 r18
      • 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 r18
    • 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 r4c162
  • Physical activity
    • Goal of 150 minutes or more per week of moderate-intensity exercise undertaken in 3 to 5 sessions throughout the week r2c163
    • Program including both aerobic and resistance training is preferred c164c165
    • Also encourage nonexercise and active leisure activity to reduce sedentary behavior r2c166
    • 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:
    • Goal setting: set a weight loss goal of 10% body weight loss in 6 months for patients with obesity; an intermediate goal of 3% to 5% weight loss in 3 months may be helpful c167
    • Self-monitoring: record daily food and exercise and measure weight at regular intervals (eg, weekly) c168c169c170c171
    • Stress reduction, stimulus control, and problem-solving strategies c172c173c174
    • Participation 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) r4c175c176
      • Electronically or telephonically delivered programs with personal feedback from a trained interventionist
      • Commercial programs can be prescribed if evidence of safety and efficacy is reliable
    • 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 c177c178c179c180
General explanation r19
  • Comprises a set of surgical procedures performed in people with obesity 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
  • 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 r4r15
  • Most bariatric surgical procedures are performed through a laparoscopic approach owing to lower early postoperative mortality and morbidity;r15 only rarely is open surgery necessary
Indication r15
  • 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 r20
  • 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;r16 one large study found 0.3% within 30 daysr20 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% r16
  • 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 r16
    • Additional complications of hypoalbuminemia, fat malabsorption, and liver dysfunction
Interpretation of results
  • Benefits include weight loss, diabetes remission, cardiovascular risk reduction, and reduced mortality r15

Comorbidities

  • All patients with obesity should be evaluated for obesity-related comorbidities and counseled regarding their increased risk of cardiovascular disease
  • Cardiovascular disease c181
    • Obesity management considerations: r2
      • Orlistat is preferred according to 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 r2c182d5
    • 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
    • ACE inhibitors or angiotensin receptor blockers should be used as first line drugs for blood pressure control
  • Diabetes c183d6
    • Select a regimen for diabetes management to include drugs that have favorable effects on body weight where possible;r21metformin is the first line agent for diabetes and obesityr10
      • 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 c184d7
    • 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 r22
    • Limited evidence that progestin-only contraceptives are associated with weight gain (mean weight gain is less than 2 kg) r23
    • 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 with BMI higher than 27 kg/m², but evidence is conflicting
  • Pregnant patients
    • Pharmacologic and surgical therapies for obesity are contraindicated during pregnancy r21r24
    • Minimum waiting period of 12 to 18 months after bariatric surgery is recommended before attempting pregnancy r24

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)r4r4r10c185c186
  • Efficacy and adverse effects of pharmacotherapy should be assessed at least monthly for the first 3 months, then at least every 3 months thereafter r10c187c188
  • Long-term follow-up consists of measuring weight and calculating BMI at least annually r4c189

Complications and Prognosis

Complications

  • Obesity-related conditions affect almost every system and include: r2
    • Hypertension c190
    • Cardiovascular disease c191
    • Type 2 diabetes/prediabetes c192c193
    • Metabolic syndrome c194
    • Dyslipidemia c195
    • Nonalcoholic fatty liver disease
      • Nonalcoholic steatohepatitis r15c196
    • Osteoarthritis c197
    • Obstructive sleep apnea c198
    • Obesity-hypoventilation syndrome r15c199
    • Worsening asthma/obstructive airway disease c200c201
    • Polycystic ovary syndrome c202
    • Depression c203
    • Gastroesophageal reflux disease c204
    • Female infertility c205
    • Male hypogonadism c206
    • Urinary stress incontinence c207
    • Gallbladder disease r25c208
    • Pseudotumor cerebri r15c209
    • Venous stasis r15c210
  • Obesity is also associated with an increased risk of certain types of cancer r25

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

Screening tests

  • Measure weight and height; calculate BMI r4c215
  • Assess diet, physical activity, and sedentary behaviors r4c216c217

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 r4c218c219c220
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