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    Obesity in Adults

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    Dec.25.2024

    Obesity in Adults

    Synopsis

    Key Points

    • Obesity is defined by excess of body adiposity
    • Obesity is clinically diagnosed based on BMI, which represents the relationship between height and weight taking into account age, ethnicity, fluid status, and muscularity
    • Based on the limitations inherent to BMI, diagnosis should also consider waist circumference and/or waist-hip ratio
    • Overweight is defined as BMI between 25 and 29.9 kg/m²
    • Obesity is defined as BMI of 30 kg/m² or higher
    • Overweight and obesity lead to metabolic, biomechanical, and psychosocial consequences, most notably, 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 adiposity-associated diseases and complications
    • Additional investigation may be required to rule out secondary causes of overweight and obesity
    • Treatment of overweight and obesity should be comprehensive, not only focusing on weight loss but also addressing and treating cardiovascular risk factors
    • Backbone of antiobesity interventions is lifestyle modification consisting of reduced caloric intake in conjunction with increased physical activity and behavior modification therapy
      • Lifestyle interventions are indicated for all patients with BMI of 25 kg/m² or higher
    • Although the backbone of antiobesity interventions is lifestyle modification, most patients are unable to achieve sustained weight loss and will require second-level therapies such as pharmacotherapy, endoscopic bariatric procedures, and/or bariatric surgery
    • Pharmacotherapy is indicated as an adjunct to lifestyle interventions for patients with BMI of 30 kg/m² or higher and for those with BMI of 27 kg/m² or higher with at least 1 adiposity-associated disease
      • Agents include diethylpropion, phentermine, phentermine-topiramate, naltrexone-bupropion, liraglutide, semaglutide, and orlistat
    • Endoscopic bariatric procedures are indicated as an adjunct to lifestyle interventions for patients with BMI of 30 kg/m² with or without adiposity-associated diseases; their long-term benefits remain to be established
    • Bariatric surgery is indicated as an adjunct to lifestyle interventions for patients with the following:
      • BMI of 40 kg/m² or higher
      • BMI of 35 to 39.9 kg/m² with at least 1 adiposity-associated disease
      • BMI of 30 to 35 kg/m² with metabolic syndrome or suboptimal diabetes control despite adequate medical therapy
    • Obesity is a chronic and relapsing disease that requires long-term treatment to avoid weight regain

    Urgent Action

    • Evaluate all patients with obesity for adiposity-associated diseases 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 having obesity; 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 r1

    • Obesity is a chronic and relapsing disease defined by an excess of body fat
    • In clinical practice, obesity is diagnosed based on the BMI, taking into account age, ethnicity, fluid status, and muscularity
      • Calculated from height and weight with the following formula: BMI = weight (kg)/height (m²)
    • Overweight and obesity are defined as follows:
      • Overweight: BMI of 25 to 29.9 kg/m²
      • Obesity: BMI of 30 kg/m² or higher
    • Spectrum of overweight and obesity is associated with metabolic, biomechanical, oncologic, and psychosocial consequences, thus posing a significant health burden

    Classification

    • International obesity classification based on BMI r1
      • Normal weight: BMI of 18.5 to 24.9 kg/m²
      • Overweight: BMI of 25 to 29.9 kg/m²
      • Obesity class 1: BMI of 30 to 34.9 kg/m²
      • Obesity class 2: BMI of 35 to 39.9 kg/m²
      • Obesity class 3 or severe obesity: BMI of 40 kg/m² or higher
      • BMI cutoff points are defined differently for people of Asian descent based on the variability in body composition and the cardiometabolic risks conferred at a lower BMI r2
        • Normal weight: BMI of between 18.5 and 22.9 kg/m²
        • Overweight: BMI of between 23 and 27.4 kg/m²
        • Obesity: BMI of 27.5 kg/m² or higher
        • People of Asian descent are at risk of underdiagnosing or of a delayed diagnosis of obesity due to failure to consider the adjusted BMI cutoff values in this population
    • Phenotypic classification r3r4r5
      • Abdominal or central obesity (upper-body obesity; "apple-shaped" body)
        • Regional and ethnic variations exist
          • Defined in some populations as waist circumference of 94 cm or higher in males and 80 cm or higher in females
          • In the United States and Canada, defined as waist circumference larger than 102 cm in males and larger than 88 cm in females
            • In people of Asian descent, defined as waist circumference of 85 cm or higher in males and 80 cm or higher in females (74 cm or higher in females according to some references)
        • Waist-hip ratios of greater than 0.9 in males and greater than 0.85 in females also correlate with increased cardiovascular risk
      • Hip-thigh-gluteal obesity (lower-body obesity; "pear-shaped" body)
        • Correlated with lower cardiovascular risk than in central obesity; not protective and not equal in risk with healthy weight (as often described), but risk is lower compared with that of central obesity
    • Etiologic classification r6
      • Primary obesity, also known as common or polygenic obesity
        • Most common form of obesity
        • Imbalance in energy intake and expenditure leads to accumulation of excess adipose tissue
        • Multifactorial causation with 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
        • Alteration in single gene leads to early onset of severe obesity in childhood
        • Most common is variant in MC4R (melanocortin 4 receptor); other forms include leptin deficiency, leptin receptor variants, and deficiency of POMC (pro-opiomelanocortin) r7

    Diagnosis

    Clinical Presentation

    History

    • Ask for permission to discuss weight r8
    • 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
      • History of mental health disorders
    • Obtain information about lifestyle habits that may be contributory c8
      • Current diet
        • Assess eating behaviors (eg, substantial portions, liquid caloric consumption, eating out, night eating)
        • If possible, obtain 24-hour diet recall
      • Current physical activity level
      • Use of supplements or OTC diet aids c9
      • Sleep (amount and quality) c10
    • Identify medications that contribute to weight gain r9
    • Ask about symptoms associated with secondary causes of or risk factors for obesity r9
      • Snoring or disrupted sleep with daytime drowsiness may be a sign of sleep apnea
      • Exercise intolerance or deconditioning may be a sign of cardiovascular or respiratory disease
      • Joint pain that may limit activity
      • Fatigue with dry skin, poor appetite, and cold intolerance may be signs of hypothyroidism
      • Central adiposity, supraclavicular and dorsocervical fullness, moon facies, wide and violaceous striae, thinning of skin, and easy bruising may be signs of excess cortisol secretion
    • Obtain information about history of adiposity-associated diseases, or assess for the presence of signs and/or symptoms of adiposity-associated diseases r10
      • Cardiometabolic diseases and cardiovascular risk factors
        • Hypertension
        • Diabetes
        • Dyslipidemia
        • Coronary artery disease
        • Other atherosclerotic disease (eg, peripheral vascular disease, carotid artery disease, stroke, transient ischemic attack)
        • Nonalcoholic fatty liver disease
        • Cigarette smoking
        • Family history of premature coronary artery disease
      • Mechanical
        • Sleep apnea
        • Gastroesophageal acid reflux
        • Osteoarthritis or joint pain
        • Intracranial hypertension (pseudomotor cerebri)
      • Malignancy
        • Esophageal adenocarcinoma
        • Gastric
        • Colorectal
        • Hepatic
        • Pancreatic
        • Breast (in postmenopausal females)
        • Endometrial
        • Ovarian
    • Assess for barriers to obesity treatment r8

    Physical examination r7r11

    • Weight and height
      • Calculate BMI from height and weight: BMI = weight (kg)/height (m²)
        • Overweight: BMI of 25 to 29.9 kg/m c11
        • Obesity: BMI of 30 kg/m² or higher c12
        • BMI thresholds are defined differently for people of Asian descent (overweight is defined as BMI between 23 and 27.4 kg/m² and obesity as BMI of 27.5 kg/m² or higher)
    • Waist circumference r12
      • Measure waist circumference midway between lowest palpable rib and iliac crest
        • In the United States and Canada, waist circumference larger than 102 cm in males and larger than 88 cm in females may indicate a higher risk of adiposity-related diseases than BMI alone c13c14
          • Among people of Asian descent, waist circumference of 85 cm or higher in males and 80 cm or higher in females (74 cm or higher in females according to some references) should be considered abdominal obesity
      • Waist-hip ratio (ie, waist circumference over hip circumference)
        • Ratios greater than 0.9 in males and greater than 0.85 in females are indicative of increased abdominal adiposity and represent high cardiovascular risk c15
        • Can be used as a surrogate measure of obesity when BMI interpretation is limited
          • 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 having overweight or obesity; include waist-hip ratio in their assessment
    • Vital signs
      • Blood pressure level may be elevated c16
      • Ensure appropriate cuff size is used for arm circumference
    • Skin findings
      • Intertrigo is common with large skin folds c17
      • Violaceous striae may be a sign of hypercortisolism c18
      • Acanthosis nigricans and skin tags may indicate insulin resistance c19c20
      • Severe acne with hirsutism suggests polycystic ovary syndrome c21c22
    • Signs associated with underlying causes or complications of obesity include:
      • Carotid bruits can represent carotid artery disease
      • Abnormal gait; hip, knee, or foot tenderness; or limited range of motion in hip or knee c23c24c25c26c27c28
      • Hepatomegaly or right upper quadrant tenderness c29c30
      • Goiter may be associated with hypothyroidism c31
      • Cushingoid appearance: moon facies, supraclavicular and dorsocervical fat pads, thinning of the skin, easy bruising, and proximal muscle weakness c32c33
      • Dependent edema may be present in ankles and feet c34

    Causes and Risk Factors

    Causes

    • Primary obesity is caused by complex relationships between genetics, eating behaviors, physical activity, and environmental factors r6c35c36c37c38
      • Most common form of obesity
      • Multifactorial causation with polygenic basis
      • Genome-wide association studies have identified multiple permissive genes associated with weight and BMI
      • Results from the interaction between permissive gene variants and environmental factors
      • Imbalance in energy intake and expenditure leads to accumulation of excess adipose tissue
    • Secondary obesity due to a variety of disease states, including: r9
      • Endocrine
        • Hypothyroidism
        • Growth hormone deficiency
        • Hypogonadism
        • Hypercortisolism
        • Pseudohypoparathyroidism
        • Polycystic ovary syndrome
      • Psychological
        • Depression (when associated with emotional eating, overeating, or binge eating) c39
        • Eating disorders c40
      • Neurologic
        • Hypothalamic dysfunction c41
        • Cranial irradiation c42
        • Brain tumors c43
        • Traumatic brain injury c44
      • Medications that may contribute to excess adiposity include:
        • Anticonvulsants c45
        • Antipsychotics c46
        • β-Blockers c47
        • Diabetes medications
          • Insulin c48
          • Sulfonylureas c49
          • Thiazolidinediones c50
        • Glucocorticoids c51
        • Oral contraceptives c52
        • Tricyclic antidepressants c53
    • Monogenic obesity r13
      • Affects a minority of patients (less than 1%)
      • Alteration in a single gene leads to early onset of severe obesity in childhood
      • Clinically, monogenic obesity can be syndromic or nonsyndromic
        • Nonsyndromic obesity
          • Variant of MC4R (melanocortin 4 receptor) is associated with severe early-onset obesity, tall stature, and hyperphagia; most common monogenic risk factor
          • Leptin deficiency and LEPR variants (leptin receptor) are associated with severe early-onset obesity and hypogonadotropic hypogonadism
          • Deficiency of POMC (pro-opiomelanocortin) is associated with severe early-onset obesity, low plasma cortisol level, and skin and hair abnormalities
          • Variants in PCSK1 (proprotein convertase subtilisin/kexin type 1) are associated with severe early-onset obesity and low insulin and cortisol levels
          • Abnormalities in genes associated with hypothalamic development (eg, SIM1, BDNF, NTRK2) have been associated with obesity in a small number of cases
        • Syndromic obesity
          • Several genetic syndromes are associated with obesity and neurodevelopmental abnormalities and are typically identified in childhood
            • Prader-Willi syndrome
            • Bardet-Biedl syndrome
            • Alström syndrome
            • Wolfram syndrome
            • Beckwith-Wiedemann syndrome
            • WAGRO syndrome
            • Carpenter syndrome
            • Cohen syndrome
            • Down syndrome
            • MEHMO syndrome
            • MOMO syndrome
            • Smith-Magenis syndrome
            • Wilson-Turner syndrome
            • Börjeson-Forssman-Lehmann syndrome

    Risk factors and/or associations

    Age r14
    • Although older age was thought to be a risk factor for obesity, based on 2017 to 2018 data from NHANES (National Health and Nutrition Examination Survey), the prevalence of obesity is similar across adulthood
      • 20 to 39 years old: 40% c54c55c56
      • 40 to 59 years old: 44.8%
      • 60 years or older: 42.8%
    Sex r15
    • According to the latest NHANES data, the prevalence of overweight is higher among US adult males than in females (34.1% versus 27.5%); however, the prevalence of obesity is similar between sexes r14r16c57c58
      • Prevalence of class 3 obesity is greater in females than in males (11.5% versus 6.9%)
    Ethnicity/race r15
    • In the United States, according to the 2017 to 2018 NHANES data, the prevalence of obesity was highest among adults of non-Hispanic Black (49.6%), Hispanic (44.8%), and non-Hispanic White descent (42.2%) and lowest among those of non-Hispanic Asian American descent (17.4%) r16c59c60c61c62
    Other risk factors/associations r17
    • Sedentary lifestyle c63
    • Fast-food consumption c64
    • Increased intake of sugar-sweetened beverages c65
    • Early-life factors (eg, parental BMI, birth weight, breastfeeding versus formula feeding) may influence childhood obesity, which is associated with adult obesity c66c67c68c69d1

    Diagnostic Procedures

    Primary diagnostic tools r7r18

    • Measure height and weight and calculate BMI at least annually c70
      • Diagnose obesity in patients with BMI of 30 kg/m² or higher and overweight in those with BMI between 25 and 29.9 kg/m² c71c72
    • Also measure waist circumference in patients who are overweight or have obesity and who have BMI less than 35 kg/m²; this measurement helps quantify cardiometabolic disease risk c73
    • Include history, review of systems, and physical examination in the initial evaluation to assess for adiposity-related diseases c74c75
    • Given a strong association between overweight and obesity and cardiometabolic risk factors, all patients should have fasting lipid panel, glucose, hemoglobin A1C, and liver enzymes levels assessed c76c77c78c79c80
    • Additional investigations may be indicated for evaluation of specific comorbidities or complications, including:
      • Endocrine evaluation if specific endocrine causes of obesity are suspected (eg, TSH for thyroid disease evaluation)
      • Overnight oximetry or polysomnography if sleep apnea is suspected c81
      • Abdominal ultrasonography, FibroScan, or MRI for nonalcoholic fatty liver disease c82
      • Abdominal ultrasonography for polycystic ovary syndrome

    Other diagnostic tools r7r18

    • Bioelectrical impedance analysis, skinfold measurement, and DXA are alternative methods to measure adiposity c83c84c85
      • Not recommended for routine clinical use

    Differential Diagnosis

    Most common

    • Secondary obesity c86
      • Obesity may be accompanied by signs and symptoms of underlying disorder (eg, hypothyroidism, hypercortisolism) or associated with medication use c87c88c89
      • Differentiate on the basis of history, physical examination findings, and laboratory test results (eg, thyroid function tests, cortisol levels) as directed by clinical findings
    • Monogenic obesity c90
      • Characterized by severe early-onset obesity starting in childhood
      • Suspect in patients with history of unexplained weight gain from infancy and who were in the 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 c91
      • Obesity develops in childhood in the context of various neurodevelopmental syndromes, including trisomy 21 (Down syndrome), Prader-Willi syndrome, and Bardet-Biedl syndrome, among others
      • Differentiate on the basis of known diagnosis of specific syndrome or history and physical examination showing characteristic dysmorphic and neurodevelopmental features

    Treatment

    Goals

    • Reduce weight and maintain it within recommended range
    • Prevent or reverse adiposity-related diseases

    Disposition

    Admission criteria

    • Hospital admission is required for patients undergoing bariatric surgical procedures

    Recommendations for specialist referral

    • All patients may benefit from consultation with an obesity medicine specialist
    • Refer to an endocrinologist if 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 or BMI higher than 30 kg/m² with an adiposity-associated disease who are interested in bariatric surgery

    Treatment Options

    General considerations r7r8r18

    • Provide holistic treatment approach, emphasizing that treatment of obesity not only results in weight loss but also in improvement of adiposity-related diseases
    • Identify contributing factors and secondary causes of obesity and barriers to treatment
    • Minimize use of weight-promoting medications
    • Lifestyle modification is the backbone of antiobesity interventions; however, most patients are not able to achieve sustained weight loss with lifestyle modification alone and will require second-level therapies, such as pharmacotherapy, endoscopic bariatric procedures, and/or bariatric surgery

    Lifestyle interventions are considered for all patients with BMI of 25 kg/m² or higher and encompass medical nutrition therapy, physical activity, and behavioral therapy r8r18

    • Medical nutrition therapy r19r20r21
      • Caloric restriction is key
        • 1200 to 1500 kcal/day for females and 1500 to 1800 kcal/day for males r19
        • Alternatively, 500- to 750-kcal deficit from estimated or measured resting energy expenditure
        • 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
      • There is no evidence to suggest that any particular diet is superior to another
      • Macronutrient composition has negligible effect on weight loss outcomes
        • Protein intake of 30% or at least 1.2 g/kg of body weight has favorable effects on body composition (ie, limits lean mass loss)
      • Dietary recommendations should be based on patients' preference with the goal of long-term adherence
      • Mediterranean diet and low-carb diet are the only diets with evidence supporting their benefits in cardiovascular disease, cardiovascular mortality, and all-cause mortality
    • Physical activity r22
      • Goal is to exercise 150 minutes weekly at moderate intensity (able to speak in full sentences but not able to sing) undertaken in 3 to 5 sessions throughout the week r11
        • An alternative is to achieve 10,000 steps daily
      • Preferred program includes both aerobic and resistance training
      • Also encourage nonexercise and active leisure activity to reduce sedentary behavior
      • Start gradually to avoid injury; increase time and intensity slowly and as tolerated
      • Consider referral to physical therapy or exercise physiology for patients who do not exercise regularly
    • Behavioral modification therapy r23r24
      • Delivered by trained professionals, consists of following:
        • Setting goals: set weight loss goal of 10% body weight loss in 6 months; intermediate goal of 3% to 5% weight loss in 3 months may be helpful
        • Self-monitoring: calorie consumption and activity tracking
        • Reducing stress, controlling stimulus, and using problem-solving strategies
      • Consider for all patients as enhances adherence to medical nutrition therapy and exercise

    Second-level therapies are considered for all patients in whom lifestyle modification alone fails to achieve weight loss goals and include pharmacotherapy, endoscopic bariatric procedures, and bariatric surgery r11

    • Pharmacotherapy is indicated as an adjunct to lifestyle interventions for patients with BMI of 30 kg/m² or higher and for those with BMI of 27 kg/m² or higher with at least 1 adiposity-associated disease
    • Endoscopic bariatric procedures are indicated as an adjunct to lifestyle interventions for patients with BMI of 30 kg/m² with or without adiposity-associated diseases
    • Bariatric surgery is indicated as an adjunct to lifestyle interventions for patients with BMI of 40 kg/m² or higher, for those with BMI of 35 to 39.9 kg/m² with at least 1 adiposity-associated disease, and for those with BMI of 30 to 35 kg/m² with metabolic syndrome or suboptimal diabetes control despite adequate medical therapy

    Pharmacotherapy r25

    • Antiobesity medications alter pathophysiologic pathways that lead to overweight and obesity and reinforce behavioral changes that promote weight loss; weight loss will be minimal without concurrent lifestyle changes r26
    • Agents have various mechanisms of action: influencing appetite and satiation (eg, diethylpropion, phentermine, phentermine-topiramate, naltrexone-bupropion, liraglutide, semaglutide, setmelanotide, tirzepatide) and reducing dietary fat absorption (orlistat) r26
    • Treatment with antiobesity medications has beneficial effects on adiposity-associated diseases
    • Prescribing considerations r27
      • Selection of a particular medication is individualized based on medical history, presence of contraindications, patient preferences, and costs r28r29
      • Dose titration is based on efficacy and tolerability to recommended maximum approved dose
      • Weight loss response is heterogenous
      • If the regimen is ineffective (ie, weight loss less than 5% of body weight after 3 months at maximum tolerated dose) or if there are safety or tolerability issues at any time, discontinue the medication and consider an alternative or referral to a bariatric specialist
      • Discontinuation of antiobesity medications leads to weight regain in most patients; therefore long-term use is required for weight loss maintenance
    • FDA-approved medications for treatment of obesity include:
      • Dual GLP-1/GIP agonist: tirzepatide r30
        • Approved for long-term use (ie, weight loss and maintenance of weight loss)
        • Although no head-to-head trials comparing all antiobesity medications, based on pivotal trials, this is likely the most effective medications currently approved for weight loss (23% total body weight loss after 16 months)
      • GLP-1 receptor agonist: liraglutide or semaglutide r31r32r33
        • Approved for long-term use (ie, weight loss and maintenance of weight loss)
        • Semaglutide is superior to liraglutide in terms of weight loss, administration, and cost effectiveness
        • Studies show total body weight loss of 6.7% to 9.2% with liraglutide and 14.9% with semaglutide after 1 year of treatment r31r33r34
      • Drugs that alter fat digestion: orlistat r35
        • Approved for long-term use (ie, weight loss and maintenance of weight loss)
        • Studies show total body weight loss of 6.4% to 11.3% after 1 year of treatment r35r36
      • Sympathomimetic drugs: benzphetamine, diethylpropion, phendimetrazine, and phentermine
        • Approved for short-term use only (3 months)
        • Limited role in treatment of obesity because discontinuing the medication leads to weight regain
        • Although they are schedule IV drugs suggesting potential for abuse, this is rare
        • Diethylpropion r37c92
          • Weight loss after 6 months: 9.8% (placebo-subtracted weight loss: 6.6%)
        • Phentermine r38
          • Data support its long-term safety in patients at low risk of cardiovascular disease
          • Weight loss after 1 year of treatment (used off label long term): 6% to 9% r38
      • Combination drugs: phentermine-topiramate and bupropion-naltrexone r39r40
        • Approved for long-term use (ie, weight loss and maintenance of weight loss)
        • Studies show total body weight loss after 1 year of treatment ranging from 6.7% to 14.4% for phentermine-topiramate and 6.7% to 11.5% for bupropion-naltrexone and maintenance of weight loss after 1 year r39r40r41r42r43r44
    • Accompanying table summarizes indications, dosages, safety concerns, adverse effects, and special considerations for antiobesity medications used for the treatment of common or polygenic obesity
      • Drug Therapy: Pharmacologic management of obesity in adults.CrCl, creatinine clearance.
        *Reevaluate therapy at 3 to 4 months and discontinue if weight loss criteria are not met.
        ‡Cognitive impairment consists of impairment of concentration, difficulty with memory, and speech or language problems.
        §Suicidal behavior and ideation have been reported in patients taking bupropion for smoking cessation or topiramate for seizures. Although these effects are not reported in trials of weight management, patients should be closely monitored for these effects.        Data from Garvey WT et al; Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines: American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract. 22(suppl 3):1-203, 2016; Kim B et al: Current long-term pharmacotherapies for the management of obesity. J Obes Metab Syndr. 29(2):99-109, 2020; Saxenda (liraglutide) injection. Package insert. Novo Nordisk Inc; 2020; Marso SP et al: Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 376(9):891-2, 2017; Ozempic (semaglutide solution for injection). Package insert. Novo Nordisk Inc; 2020; Siebenhofer A et al: Long-term effects of weight-reducing drugs in people with hypertension. Cochrane Database Syst Rev. 3:CD007654, 2016; Davidson MH et al: Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. JAMA. 281(3):235-42, 1999; Tonstad S et al: The effect of the gastrointestinal lipase inhibitor, orlistat, on serum lipids and lipoproteins in patients with primary hyperlipidaemia. Eur J Clin Pharmacol. 46:405-10, 1994; Xenical (orlistat) capsules. Package insert. Genentech USA Inc; 2016; Alli (orlistat) capsules. Package insert. GSK Consumer Healthcare; 2016; Weir MA et al: Orlistat and acute kidney injury: an analysis of 953 patients. Arch Intern Med. 171:703-4, 2011; FDA: Completed safety review of Xenical/Alli (Orlistat) and severe liver injury. FDA website. Accessed October 30, 2023. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fda-drug-safety-communication-completed-safety-review-xenicalalli-orlistat-and-severe-liver-injury; Contrave (naltrexone HCl and bupropion HCl) extended-release tablets. Package insert. Nalpropion Pharmaceuticals Inc; 2020; Qsymia (phentermine and topiramate extended-release). Package insert. Vivus Inc; 2020; Garris SS et al: Impact of topiramate on serum bicarbonate concentrations in adults. Ann Pharmacother. 39:424-6, 2005; Phentermine hydrochloride capsule. Package insert. KVK-Tech Inc; 2018; Phentermine hydrochloride tablet. Package insert. Epic Pharma LLC; 2020; Lomaira (phentermine hydrochloride). Package insert. KVK-Tech Inc; 2016; and Zepbound (tirzepatide) injection. Package insert. Eli Lilly and Company; 2023.
        MedicationTherapeutic useDosageSafety concernNotable adverse reactionsSpecial considerations
        Antidiabetic agents
        Liraglutide*Preferred in patients who
        report inadequate meal satiety and patients with type 2 diabetes; may be good
        option for those with anxiety, depression, or seizure disorder        		0.6 mg subcutaneously once
        daily for 1 week, then increase by 0.6 mg/week until target dose is reached.
        Maximum dose for weight management = 3 mg subcutaneously once daily        		BOXED WARNING: causes thyroid C-cell tumors in rodents; human
        risk is unknown. Contraindicated in patients with personal or family history

        Monitor renal function in
        patients reporting severe adverse gastrointestinal reactions when initiating or
        increasing dose; discontinue therapy if patients develop volume depletion

        Drug interactions: may need to avoid or adjust dosage of certain drugs
        		Common
        Abdominal pain
        Constipation
        Diarrhea
        Dyspepsia
        Heart rate increase
        Injection site reaction
        Nausea
        Vomiting

        Rare, but serious
        Cholelithiasis
        Pancreatitis
        Renal failure
        Serious hypersensitivity reactions
        Suicidal behavior and ideation        		Monitor heart rate at
        regular intervals

        Monitor blood glucose level in patients with type 2 diabetes

        May not be good option for patients with needle
        aversion
        SemaglutidePreferred in patients with
        type 2 diabetes; may be good option in patients with cardiovascular disease,
        hyperlipidemia        		Titrate to target dose over
        17 weeks. Administer doses subcutaneously
        Weeks 1-4: 0.25 mg once weekly
        Weeks 5-8: 0.5 mg once weekly
        Weeks 9-12: 1 mg once weekly
        Weeks 13-16: 1.7 mg once weekly
        Week 17 and onward: 2.4 mg once weekly

        If a given dose is not tolerated, consider slowing dose escalation        		BOXED WARNING: causes thyroid C-cell tumors in rodents; human
        risk unknown. Contraindicated in patients with personal or family history

        Monitor renal function in patients reporting severe adverse gastrointestinal reactions
        when initiating or increasing dose; discontinue therapy if patients develop
        volume depletion

        Drug interactions: may need to avoid or adjust dosage of certain drugs        		Common
        Abdominal pain
        Constipation
        Diarrhea
        Headache
        Heart rate increase
        Injection site reaction
        Nausea
        Vomiting

        Rare, but serious
        Cholelithiasis
        Pancreatitis
        Renal failure
        Serious hypersensitivity reactions        		Monitor blood glucose level and
        for retinopathy in patients with type 2 diabetes

        May not be good option for patients with needle aversion
        TirzepatideMay be preferred in patients with type 2 diabetes2.5 mg subcutaneously once weekly for 4 weeks, then increase by 2.5 mg/week every 4 weeks until target dose is reached. Recommended maintenance dosages for weight management = 5, 10, or 15 mg once weeklyBOXED WARNING: causes thyroid C-cell tumors in rodents; human risk is unknown. Contraindicated in patients with personal or family history

        Monitor renal function in patients reporting severe adverse gastrointestinal reactions that could lead to volume depletion        		Common
        Abdominal pain
        Alopecia
        Constipation
        Diarrhea
        Dyspepsia
        Eructation
        Fatigue
        Gastroesophageal reflux disease
        Injection site reaction
        Nausea
        Vomiting

        Rare, but serious
        Acute kidney injury
        Acute pancreatitis
        Cholecystitis
        Serious hypersensitivity reactions
        Suicidal behavior and ideation        		Monitor blood glucose level and for retinopathy in patients with type 2 diabetes

        May not be good option for patients with needle aversion
        Lipase inhibitor
        OrlistatPreferred in patients with
        anxiety or depression, cardiovascular disease, hyperlipidemia, hypertension,
        substance use disorders        		60-120 mg PO 3 times daily

        Administer with each fat-containing main meal, during meal, or up to 1 hour
        after meal        		Do not use in patients with
        cholestasis, chronic malabsorption, or those with or at risk of oxalate
        nephrolithiasis

        Drug interactions: separate administration of certain other oral medications
        due to decreased absorption        		Common
        Abdominal pain
        Fecal incontinence
        Fecal urgency
        Flatulence with discharge
        Steatorrhea
        Vitamin deficiency of fat-soluble vitamins

        Rare but serious
        Hepatotoxicity        		Supplement with a daily
        multivitamin containing vitamins A, D, E, K, and β-carotene at least 2 hours
        before or after orlistat

        Not a good selection for patients unable to modify dietary fat intake
        Opioid antagonist/aminoketone antidepressant combination
        Naltrexone-bupropion extended-release*May be preferred in
        patients who describe cravings for food and/or addictive behaviors related to
        food        		Titrate to target dose over
        4 weeks
        Week 1: 1 tablet (8-mg naltrexone/90-mg bupropion) PO once daily in morning
        Week 2: 1 tablet PO twice daily
        Week 3: 2 tablets PO in morning, 1 tablet PO in evening
        Week 4: 2 tablets PO twice daily
        Max dose: 4 tablets/day (32 mg/360 mg)

        Adjust dose for moderate or severe renal impairment or moderate hepatic
        impairment        		BOXED WARNING: increased risk of suicidal thinking and
        behavior in young adults

        Contraindicated in patients with chronic opioid use, drug or alcohol
        withdrawal, eating disorder, seizure disorder, uncontrolled hypertension, or
        recent MAOI use

        Avoid use in patients with end-stage renal disease or severe hepatic impairment

        Use with caution in patients with closed-angle glaucoma

        Drug interactions: may need to avoid or adjust dosage of certain drugs        		Common
        Blood pressure increase
        Constipation
        Dizziness
        Dry mouth
        Headache
        Heart rate increase
        Insomnia
        Nausea
        Vomiting

        Rare but serious
        Hepatotoxicity
        Seizures
        Serious allergic reactions
        Suicidal thoughts and behavior§        		Measure blood pressure and
        heart rate before treatment and at regular intervals during therapy
        Sympathomimetic amine anorectic/antiepileptic combination
        Phentermine-topiramate extended-release*Preferred in otherwise
        healthy patients who could benefit from appetite suppression; may be used in
        those with seizure disorder        		Initial dose: 3.75 mg/23 mg
        (phentermine-topiramate) PO once daily in the morning for 14 days

        Titrate based on response: 7.5 mg/46 mg PO once daily for 12 weeks, then 11.25
        mg/69 mg PO once daily for 14 days

        Max dose: 15 mg/92 mg PO once daily

        Adjust dose for CrCl < 50 mL/minute or moderate hepatic impairment
        (Child-Pugh class B)        		Contraindicated in patients
        with glaucoma, hyperthyroidism, pregnancy, and recent MAOI use

        Avoid use in patients with end-stage renal disease on dialysis or severe
        hepatic impairment

        Use with caution in patients with history of kidney stones

        Drug interactions: may need to avoid or adjust dosage of certain drugs        		Common
        Cognitive impairment‡
        Constipation
        Dizziness
        Dry mouth
        Dysgeusia
        Headache
        Insomnia
        Mood disorders
        Paresthesia

        Rare, but serious
        Acute myopia/glaucoma
        Metabolic acidosis
        Oligohidrosis
        Suicidal thoughts and behavior§
        		Discontinue gradually;
        abrupt discontinuation can precipitate seizures

        Pregnancy testing recommended before initiation and monthly thereafter
        Sympathomimetic amine anorectics
        Phentermine 15- to 37.5-mg
        capsules and tablets        		FDA-approved for short-term
        use only        		15-37.5 mg PO once daily
        every morning before or 1 to 2 hours after breakfast or 18.75 mg in the morning
        and 18.75 mg later in the day (not in late evening)

        Adjust dose for CrCl < 30 mL/minute        		Contraindicated in patients
        with anxiety or agitation, insomnia, glaucoma, history of cardiovascular
        disease, history of drug misuse, hyperthyroidism, uncontrolled hypertension, or
        recent MAOI use

        Avoid use in patients with CrCl < 15 mL/minute or end-stage renal disease on
        dialysis

        Drug interactions: may need to avoid or adjust dosage of certain drugs        		Common
        Anxiety
        Blood pressure increase
        Constipation
        Dizziness
        Dry mouth
        Headache
        Heart rate increased
        Insomnia
        Irritability
        Palpitations

        Rare, but serious
        Pulmonary hypertension
        Valvular heart disease
        Phentermine 8-mg tabletsFDA-approved for short-term
        use only        		4-8 mg PO 3 times daily, 30
        minutes before meals        		Contraindicated in patients
        with anxiety or agitation, insomnia, glaucoma, history of cardiovascular
        disease, history of drug misuse, hyperthyroidism, uncontrolled hypertension, or
        recent MAOI use

        Use with caution in patients with renal impairment

        Drug interactions: may need to avoid or adjust dosage of certain drugs        		Common
        Anxiety
        Blood pressure increase
        Constipation
        Dry mouth
        Headache
        Heart rate increased
        Insomnia
        Palpitations

        Rare, but serious
        Pulmonary hypertension
        Valvular heart disease

    Endoscopic bariatric procedures r45

    • Indicated as an adjunct to lifestyle interventions for patients with BMI of 30 kg/m² with or without adiposity-associated diseases
    • Currently FDA-approved endoscopic procedures are intragastric balloon and sleeve gastroplasty
    • Data are limited on long-term outcomes
    • Patients interested in these procedures should be referred to a gastroenterologist

    Bariatric surgery

    • Bariatric surgery comprises a set of surgical procedures performed in patients with obesity to achieve and sustain substantial weight loss
      • Common bariatric surgical procedures include:
        • Purely restrictive procedures: the adjustable gastric banding and vertical sleeve gastrectomy
          • Adjustable gastric banding is no longer recommended based on the complications and long-term failure
        • Restrictive and malabsorptive: the Roux-en-Y gastric bypass and the biliopancreatic diversion with or without duodenal switch
    • Traditionally indicated as an adjunct to lifestyle interventions for patients with BMI of 40 kg/m² or higher, those with BMI of 35 to 39.9 kg/m² with at least 1 adiposity-associated disease, and for those with BMI of 30 to 35 kg/m² with metabolic syndrome or suboptimal diabetes control despite adequate medical therapy r7r46
    • Newer guidelines recommend a more aggressive management; however, this has not yet become the norm in clinical practice
      • 2022 American Society for Metabolic and Bariatric Surgery/International Federation for the Surgery of Obesity and Metabolic Disorders guidelines recommend bariatric surgery for patients with BMI of 35 kg/m² or higher and for those with BMI of 30 to 35 kg/m² with at least 1 adiposity-associated disease r47
    • Bariatric surgery remains the most effective treatment of obesity r48
      • Compared with the nonsurgical treatment of obesity, bariatric surgery has the greatest efficacy, durability, and improvement in adiposity-associated diseases
      • It is the only antiobesity treatment with reliable data showing a decrease in adiposity-associated cardiovascular events and mortality, cirrhosis, end-stage renal disease, cancer, and all-cause mortality

    Drug therapy r26

    • Dual GLP-1/GIP (glucose-dependent insulinotropic polypeptide) receptor agonist
      • Tirzepatide
        • Tirzepatide Solution for injection [Weight Management]; Adults: 2.5 mg subcutaneously once weekly for 4 weeks, then 5 mg subcutaneously once weekly, initially. May increase the dose by 2.5 mg/week after at least 4 weeks; adjust dose based on clinical response and tolerability. Consider a lower maintenance dose if a higher dose is not tolerated. Usual dose: 5, 10, or 15 mg/week. Max: 15 mg/week.
    • GLP-1 receptor agonists
      • Liraglutide c93
        • Liraglutide Solution for injection [Weight Management]; Adults: 0.6 mg subcutaneously once daily for 1 week, 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
        • Semaglutide Solution for injection [Weight Management]; Adults: 0.25 mg subcutaneously once weekly for 4 weeks, then 0.5 mg subcutaneously once weekly for 4 weeks, then 1 mg subcutaneously once weekly for 4 weeks, then 1.7 mg subcutaneously once weekly for 4 weeks, and then 1.7 or 2.4 mg (recommended) subcutaneously once weekly. Consider delaying dose escalation for 4 weeks if a dose increase is not tolerated. Assess treatment response and tolerability when selecting the maintenance dose.
    • Lipase inhibitor c94
      • Orlistat
        • Prescription
          • Orlistat Oral capsule; Adults: 120 mg PO 3 times daily with each main meal containing fat.
        • OTC
          • Orlistat Oral capsule; Adults: 60 mg PO 3 times daily with each main meal containing fat. Max: 180 mg/day.
    • Sympathomimetic amines
      • Diethylpropion
        • Immediate-release
          • 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 r38c95
        • Once- or twice-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.
      • Phentermine-topiramate
        • 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.
    • Opioid antagonist–aminoketone antidepressant combination
      • Naltrexone-bupropion c96
        • 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 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.
    • Melanocortin 4 (MC4) receptor agonist
      • Setmelanotide
        • For obesity due to POMC (pro-opiomelanocortin), PCSK1 (proprotein convertase subtilisin/kexin type 1), or LEPR deficiency (leptin receptor)
          • 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.
        • 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.

    Nondrug and supportive care

    Lifestyle interventions, consisting of medical nutrition therapy, physical activity, and behavioral therapy, are recommended for all patients r8r11

    Procedures
    Bariatric surgery c97
    General explanation r49
    • Comprises a set of surgical procedures performed in patients 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 c98c99c100c101
    • Type of procedure and approach depend on goals of therapy, patient factors (eg, age, severity of obesity, risk of complications, comorbidities, behavioral and psychosocial factors, personal preferences), and local surgical expertise
    • Most bariatric surgical procedures are performed laparoscopically, because they have lower early postoperative mortality and morbidity; open surgery is only rarely
    Indication
    • Bariatric surgery is indicated for people 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 complication
      • 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
    • Newer 2022 American Society for Metabolic and Bariatric Surgery/International Federation for the Surgery of Obesity and Metabolic Disorders guidelines recommend more aggressive management with bariatric surgery indicated at the following thresholds (not yet incorporated into clinical practice): r47
      • BMI of 35 kg/m² or higher
      • BMI of 30 to 35 kg/m² with at least 1 adiposity-associated disease
    Contraindications r50
    • Absolute
      • Diseases associated with poor long-term life expectancy, unless survival improves because of weight loss
      • Uncontrolled or untreated major depression or other psychiatric illnesses
      • Active substance misuse
      • Pregnancy or breastfeeding
    • Relative
      • Portal hypertension
      • Poor myocardial reserve
      • Significant chronic obstructive pulmonary disease or respiratory dysfunction
      • History of nonadherence to medical care
      • Borderline personality disorder or bipolar disease
    Complications
    • Perioperative mortality rates are low (less than 1%)
    • Depending on type of surgery, rates of severe adverse events range from 0% to 37%; rates of reoperation range from 2% to 13%
    • Complications may occur with all bariatric procedures and include:
      • Anastomotic stricture
      • Gastrointestinal leak
      • Dumping syndrome
      • Small-bowel obstruction/internal hernia
      • Nutritional deficiencies owing to malabsorption and dietary choices
      • Thromboembolism
      • Gastric ulcer
      • Gallstones
      • Nephrolithiasis
      • Bone loss
      • Biliopancreatic diversion is associated with high peri- and postoperative complication rate; additional complications include hypoalbuminemia, fat malabsorption, and liver dysfunction

    Comorbidities

    • Evaluate all patients with obesity for adiposity-associated diseases and counsel them regarding their increased risk for cardiovascular disease
    • Cardiovascular disease r20r51r52r53c102
      • Mediterranean diet and low-fat diet decrease major adverse cardiovascular events
      • Liraglutide and semaglutide have data supporting their cardiovascular benefits in patients with type 2 diabetes, and liraglutide has data supporting its cardiovascular benefit in patients with overweight and obesity
      • Phentermine and phentermine-topiramate are contraindicated in patients with cardiovascular disease (eg, coronary artery disease that is symptomatic or that has required intervention, stroke, transient ischemic attack, arrhythmias, heart failure)
    • Hypertension r54c103d2
      • Avoid sympathomimetic pharmacotherapy for obesity (eg, phentermine or phentermine-topiramate) unless hypertension is well controlled
      • Use ACE inhibitors or angiotensin receptor blockers as first line drugs for blood pressure control
    • Diabetes r55r56c104d3
      • Select drugs to control diabetes that have favorable effects on body weight where possibler56
      • Diabetes medication classes associated with weight gain include sulfonylureas, meglitinides, thiazolidinediones, and insulin
      • Classes of diabetes medication that promote varying degrees of weight loss include metformin, GLP-1 receptor agonists, dual GLP-1/glucose-dependent insulinotropic polypeptide receptor agonist, sodium-glucose–linked transporter-2 inhibitors, and amylin mimetics
      • Diabetes medication classes that are weight neutral include dipeptidyl peptidase IV inhibitors, centrally acting dopamine agonists (bromocriptine), α-glucosidase inhibitors, and bile acid sequestrants (colesevelam)
    • Depression r11c105d4
      • 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 r2
      • BMI cutoff points are defined differently for people of Asian descent based on usual body composition; altered ranges have implications for treatment indications
        • Normal weight: BMI of 18.5 to 22.9 kg/m²
        • Overweight: BMI of 23 to 27.4 kg/m²
        • Obesity: BMI of 27.5 kg/m² or higher
    • Pregnant patients
      • Pharmacologic and surgical therapies for obesity are contraindicated during pregnancy r57
      • Advise patients to wait a minimum of 12 to 18 months after bariatric surgery before attempting pregnancy r57
    • Genetic forms of obesity r58r59r60
      • Patients with obesity due to Bardet-Biedl syndrome or to sequence variants in various genes (POMC, PCSK1, LEPR) are candidates for pharmacotherapy with setmelanotide r60
      • Setmelanotide is an MC4R agonist r61
        • Reestablishing MC4R 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 deficiency and 12.5% in those with LEPR deficiency r58
        • In another randomized controlled trial, mean percentage of weight loss after 1 year of use was 9.1% in those with Bardet-Biedl syndrome r59
    • Females of childbearing age desiring hormonal contraception (without other contraindications) r62
      • No evidence that combination hormonal contraception (estrogen plus a progestin) is associated with weight change
      • Limited evidence that progestin-only contraceptives are associated with weight gain (mean weight gain is less than 2 kg)
      • If BMI is 27 kg/m² or higher with comorbidities or 30 kg/m² or higher, recommend intrauterine device or 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
      • Pregnancy is contraindicated while using antiobesity medications
      • Phentermine-topiramate is a proven teratogenic and is part of the Risk Evaluation and Mitigations Strategy program to ensure that benefits of the treatment outweigh the risks
      • Avoid oral contraceptives after bariatric surgery, especially those with a malabsorptive component (ie, Roux-en-Y gastric bypass and biliopancreatic diversion)

    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 during a 6-month period) and at least weekly self-monitoring (weighing)r19c106c107
    • Assess efficacy and adverse effects of pharmacotherapy at least monthly for the first 3 months, then at least every 3 months thereafter c108c109
    • Long-term follow-up consists of measuring weight and calculating BMI at least annually c110

    Complications and Prognosis

    Complications

    • Excess adiposity has negative consequences in virtually every system r10
    • Adiposity-associated disease include:
      • Hypertension c111
      • Cardiovascular disease c112
      • Type 2 diabetes or prediabetes c113c114
      • Metabolic syndrome c115
      • Dyslipidemia c116
      • Spectrum of nonalcoholic fatty liver disease
      • Osteoarthritis c117
      • Obstructive sleep apnea c118
      • Obesity-hypoventilation syndrome c119
      • Worsening asthma or obstructive airway disease c120c121
      • Polycystic ovary syndrome c122
      • Depression c123
      • Anxiety
      • Gastroesophageal reflux disease c124
      • Female infertility c125
      • Male hypogonadism c126
      • Urinary stress incontinence c127
      • Gallbladder disease c128
      • Pseudotumor cerebri c129
      • Venous stasis c130
      • Gout c131
      • Cancer

    Prognosis

    • Obesity is typically a chronic and relapsing disease r63
    • Weight-reduced state leads to behavioral and metabolic adaptations that can result in weight regain, particularly if no long-term treatment is established
    • Excess adiposity is associated with increased cardiometabolic risk
      • There is a linear relation between overweight and obesity class and the risk of cardiovascular disease and mortality and the risk of all-cause mortality
    • Treatments that lead to significant and sustained weight loss reduce these risks

    Screening and Prevention

    Screening

    At-risk populations

    • Universal screening is recommended r19
      • All adults in the United States should be screened for obesity at least annually during regular medical office visits c138

    Screening tests

    • Measure weight and height to calculate BMI c139
    • Assess eating choices, behaviors, and activity

    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 adiposity-associated diseases c140c141c142
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Adolesc Med State Art Rev. 28(2):379-405, 201730416642Wharton S et al: Obesity in adults: a clinical practice guideline. CMAJ. 192(31):E875-91, 202032753461Acosta A et al: White paper AGA: POWER--Practice Guide on Obesity and Weight Management, Education, and Resources. Clin Gastroenterol Hepatol. 15(5):631-49.e10, 201728242319van der Valk ES et al: A comprehensive diagnostic approach to detect underlying causes of obesity in adults. Obes Rev. 20(6):795-804, 201930821060Yuen MMA: Health complications of obesity: 224 obesity-associated comorbidities from a mechanistic perspective. Gastroenterol Clin North Am. 52(2):363-80, 202337197879Garvey WT et al: American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive practice guidelines for medical care of patients with obesity. Endocr Pract. 22(suppl 3):1-203, 201627219496Ma WY et al: Measurement of waist circumference: midabdominal or iliac crest? Diabetes Care. 36(6):1660-6, 201323275359Huvenne H et al: Rare genetic forms of obesity: clinical approach and current treatments in 2016. Obes Facts. 9(3):158-73, 201627241181National Institute of Diabetes and Digestive and Kidney Diseases: Overweight and Obesity Statistics. NIDDK website. Updated September 2021. Accessed February 15, 2024. https://www.niddk.nih.gov/health-information/health-statistics/overweight-obesityhttps://www.niddk.nih.gov/health-information/health-statistics/overweight-obesityHales CM et al: Prevalence of obesity and severe obesity among adults: United States, 2017-2018. NCHS Data Brief. 1-8, 202032487284Ogden CL et al: Prevalence of obesity among adults and youth: United States, 2011-2014. NCHS Data Brief. 1-8, 201526633046Safaei M et al: A systematic literature review on obesity: understanding the causes and consequences of obesity and reviewing various machine learning approaches used to predict obesity. Comput Biol Med. 136:104754, 202134426171Garvey WT et al: American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity: executive summary. Endocr Pract. 22(7):842-84, 201627472012Jensen MD et al: 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and The Obesity Society. J Am Coll Cardiol. 63(25, pt B):2985-3023, 201424239920Karam G et al: Comparison of seven popular structured dietary programmes and risk of mortality and major cardiovascular events in patients at increased cardiovascular risk: systematic review and network meta-analysis. BMJ. 380:e072003, 202336990505Johnston BC et al: Comparison of weight loss among named diet programs in overweight and obese adults: a meta-analysis. JAMA. 312(9):923-33, 201425182101Petridou A et al: Exercise in the management of obesity. Metabolism. 92:163-9, 201930385379Wadden TA et al: Behavioral treatment of obesity in patients encountered in primary care settings: a systematic review. JAMA. 312(17):1779-91, 201425369490Olateju IV et al: Role of behavioral interventions in the management of obesity. Cureus. 13(9):e18080, 202134671541Mauer Y et al: Antiobesity drug therapy: an individualized and comprehensive approach. Cleve Clin J Med. 88(8):440-8, 202134341028Apovian CM et al: Pharmacological management of obesity: an Endocrine Society clinical practice guideline.  J Clin Endocrinol Metab. 100(2):342-62, 2015. Published correction appears in J Clin Endocrinol Metab. 100(5):2135-6, 201525590212FDA: Drug Safety and Availability: FDA Requests the Withdrawal of the Weight-Loss Drug Belviq, Belviq XR (Lorcaserin) From the Market: Potential Risk of Cancer Outweighs the Benefits. FDA website. Published February 13, 2020. 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