Condition Background

The most widely used and practical way to evaluate degree of overweight is by body mass index (BMI), calculated as weight in kilograms divided by height in meters squared (kg/m²). Adults with BMIs from 25 to 29.9 kg/m² are generally considered to be overweight and those with BMIs equal to or greater than 30 kg/m² are considered to have obesity.^1-3 The category of “obese” is further divided into subcategories of Class I obesity (BMI 30.0 to 34.9 kg/m²), Class II obesity (BMI 35.0 to 39.9 kg/m²), and Class III obesity (BMI ≥40 kg/m²).²

The relationship between percent body fat and BMI differs among ethnic groups.^{4, 5} Such differences have raised concerns about the appropriateness of current BMI cut-offs for all ethnic groups. However, BMI thresholds have generally been based on morbidity and mortality outcomes and not the BMI-adiposity relationship.⁴ All racial/ethnic groups have increased mortality, cardiovascular disease (CVD) risk, and type 2 diabetes risk with increasing BMI, but there may be group-specific differences in absolute risk, the level of BMI at which increased risk occurs, and the strength of the relationship (Appendix A).^6-20 In Asians, the BMI associated with increased diabetes risk^{14, 21-23} and mortality^24-27 is lower than in Caucasians, consistent with their higher body fat at a given BMI level; therefore, the World Health Organization (WHO) suggested that countries consider setting lower potential BMI action points for Asians (along the BMI continuum from 23.0 to 27.5 kg/m²).¹⁸ The evidence regarding whether current BMI cut-offs are appropriate for non-Hispanic blacks and Hispanics is mixed.^{6, 20, 28-31} Given the complexity of the relationship between BMI and ethnicity, and the limited, conflicting data, neither of the two groups that have reviewed this topic, the National Institute of Health and Care Excellence in the United Kingdom or the American Heart Association/American College of Cardiology/Obesity Society (AHA/ACC/TOS) workgroup, has recommended changing the BMI thresholds for blacks, Hispanics, or other ethnic groups.^3,23 The AHA/ACC/TOS panel noted a “critical” lack of studies on racial/ethnic differences in Western countries to determine whether different cut-points for racial/ethnic subgroups might be appropriate.

Prevalence of Overweight and Obesity

In 2013–2014, 35 percent of U.S. men and 40 percent of U.S. women were categorized as having obesity.³² About 1 in 13 Americans has a BMI of more than 40 kg/m² (Class III obesity).³³ From 2005 through 2014 there has been a significant increase in the rate of women with obesity but not men.^{32, 34, 35} When expanded to include overweight and obesity (BMI ≥25 kg/m²) the age-adjusted prevalence in 2011–2014 was 73.0 percent of U.S. men and 66.2 percent of U.S. women.³⁶

Using the standard definitions of BMI across ethnic groups, nonwhite adults have a higher prevalence of overweight and obesity than white adults. Among women, for example, the age-adjusted prevalence of obesity (BMI ≥30 kg/m²) is higher among non-Hispanic black (57.2%) and Hispanic women (46.9%) than among non-Hispanic white women (38.2%). The difference in obesity prevalence is less marked among men (38.0% in non-Hispanic black men, 37.9% in Hispanic men, and 34.7% in non-Hispanic white men).³⁵ Rates of obesity among Asian Americans are lower than other groups (12.4% in women and 12.6% in men);³⁵ however, when using the adjusted cut-off of greater than 25 kg/m² is higher (43% for U.S.-born Asians) than that of non-Hispanic whites (36%).³⁷

Burden of Disease

Overweight and obesity have been associated with an increased risk of coronary heart disease (CHD), type 2 diabetes, and cancer, even after adjustment for established risk factors (Appendix A).^38-47 Other diseases that have been associated with obesity include ischemic stroke,^{11, 48, 49} heart failure,⁴¹ atrial fibrillation/flutter,^{50, 51} venous thrombosis,⁵² gallstones,^53-55 gastroesophageal reflux disease,⁵⁶ renal disease,^{57, 58} and sleep apnea.⁵⁹ Midlife obesity has been associated with later-in-life dementia.^{60, 61} Obesity also increases the risk of developing osteoarthritis^{62, 63} and is associated with functional disability.⁶⁴ Some observational studies suggest that individuals with obesity, even those without comorbid diseases, may have a decreased quality of life (QOL) compared with individuals who are not overweight or have obesity.^65-67 As a result of the increased morbidity, there is increased use of health care services and costs among individuals with obesity.^{68, 69}

BMI has been associated with risk of death. The shape of the association appears to be J shaped with higher and lower BMIs being associated with increased mortality. However, the nadir of the curve is controversial. Obesity (BMI ≥30 kg/m²) has been associated with an increased risk of death, especially in women and adults younger than age 65 years.^{70, 71} Obesity has been estimated to advance death in the United States by 1.6 years for those with BMIs between 30 and 34.9 kg/m² and by 3.7 years for those with BMIs of 35 kg/m² and above.⁷¹ Ischemic heart disease, diabetes, cancer (especially liver, kidney, breast, gallbladder, pancreas, endometrial, prostate, and colon cancers), and renal, hepatic, and respiratory diseases are leading causes of death in those who have obesity.^{72, 73}

Whether being overweight (BMI 25 to 29.9 kg/m²) is associated with increased mortality risk has been the subject of considerable public health debate.⁷⁴ Some,^{73, 75-80} but not all,^{29, 70, 81, 82} studies have found an increased risk of death in those who are overweight (Appendix A). The difficulty in conducting these studies is that conditions leading to death may cause lower BMI rather than lower BMI causing death (reverse causation bias).^{83, 84} A recent analysis of the Nurses’ Health Study I and II and the Health Professionals Follow-Up Study attempted to avoid this problem by looking at maximum BMI over 16 years of prospective weight history. Maximum BMI in overweight, Class I obesity, and Class II obesity categories were all associated with a statistically significant increased risk for all-cause death (increased risk of 6%, 24%, and 73%, respectively). The nadir for risk for all-cause death was 22.5 to 24.9 kg/m² among all participants.⁸⁰ In addition, those who were overweight at baseline and remained so during followup did not have an increased risk of death compared with those who were normal weight during the entire observation period. In contrast, those who had obesity throughout the study (at baseline and during followup) had an increased risk of death compared with those who were not overweight or have obesity at all time points.⁸⁰

The relationship between BMI and mortality is weaker and less reliable in older adults⁸⁰ likely due to the central fat redistribution, decreased muscle mass, and decreased stature that occurs with aging (Appendix A).^85-88 While the curve still appears to be J shaped with higher and lower BMIs being associated with increased mortality, the nadir of the curve may be shifted upward, close to or even into the overweight category.^{70, 79, 80, 85, 86, 89} While the evidence is mixed regarding whether older persons with Class 1 obesity (BMI 30 to 35 kg/m²) have an increased mortality risk,^{70, 85, 89} most evidence suggests that those with Class 2 and 3 obesity (BMI ≥35 kg/m²) do have increased mortality risk.^{31, 70, 85, 89} Obesity has been associated with higher rates of physical and functional disability and functional decline in older populations,^{31, 90-92} but whether overweight is associated with physical decline is less clear.^{31, 90} The 2013 AHA/ACC/TOS report on the Management of Overweight and Obesity in Adults (published before some of these data were reported) concluded there was insufficient evidence to address the adequacy of existing BMI cut-points in adults older than age 65 years.³

The association between overweight and mortality risk may also be influenced by environmental and person-specific factors such as disease history, diet, and physical activity. Individuals with overweight but without cardiovascular risk factors, often termed “metabolically healthy,” especially those who are physically active, may not have an increased risk of mortality compared with normal-weight individuals.^93-97

There are also potential psychosocial burdens associated with having overweight or obesity and with the implementation of weight loss interventions, including weight stigma⁹⁸ and eating disorders.^99-101

Etiology and Natural History

Many factors contribute to the development of overweight and obesity.^{102, 103} Nutritional factors contributing to the growing obesity epidemic include the availability of more processed and affordable foods that are high in fat and sugar,^{104, 105} including potato chips, sugar-sweetened beverages, and processed meats.¹⁰⁶ Other factors that play an important role in this epidemic include increasingly sedentary lifestyle,¹⁰⁷ more screen time,¹⁰⁸ increased fast-food consumption,¹⁰⁹ and sleep deprivation.¹¹⁰ It is increasingly recognized that regulation of energy homeostasis and body weight is a complex process involving the central and sympathetic nervous systems, the melanocortin system, nutrient intake, gut hormones, the gut microbiome, and adipose tissue itself.^111-114 Genetic factors play a permissive role and interact with environmental factors to produce obesity.^{102, 103, 115} In terms of the natural history of obesity, weight gain in adults is a steady progression, with significant increases at points like pregnancy, development of depression/psychosocial stressors, changes in functional status due to pain/injury, or with the addition of obesogenic medications in the treatment of other conditions until about the sixth decade of life, when weight appears to stabilize and then decline with age.^{2, 116, 117}

Risk Factors

Environmental and nutritional exposures in early development may influence the risk of developing obesity later in life.¹¹⁸ Animal and human data suggest that maternal BMI and macronutrient/energy intake during gestation influence offspring appetite, metabolism, adiposity, and risk of overweight/obesity in childhood and into adulthood.^{119, 120} Maternal smoking,¹²¹ maternal gestational diabetes,¹²² and short or no exposure to breastfeeding are also associated with an increased risk of childhood obesity.¹²³ Childhood obesity increases the risk of adult obesity^{124, 125} and having an elevated BMI in early adulthood (ages 20 to 22 years) appears to increase the risk of developing obesity within 15 years. For example, in a study of the natural history of the development of obesity in young U.S. adults, 41 percent of white, 47 percent of Hispanic, and 66 percent of black women who had BMIs of 24 to 25 kg/m² at ages 20 to 22 developed obesity by ages 35 to 37 years.¹²⁶

Screening

Measurements that can be used to estimate body fat and quantify health risks include BMI, waist circumference, waist to hip ratio, bioimpedance, and dual energy x-ray absorptiometry.¹²⁷ Measuring height and weight to calculate BMI in a clinical setting is a low-cost, relatively quick, and reasonably reliable way to screen for obesity. Reference charts and BMI calculators are available to allow clinicians to determine a patient’s BMI using his/her height and weight without having to perform a manual calculation. A 2003 evidence report for the U.S. Preventive Services Task Force (USPSTF) found good-quality evidence supporting the use of BMI to identify adults with increased risk of future morbidity and mortality.¹²⁸

Patients with abdominal obesity (also called central adiposity, visceral, android, or male-type obesity) are at increased risk for heart disease, cancer, diabetes, and death.^129-134 Multiple ways of measuring central adiposity have been proposed including waist circumference, waist to hip ratio,¹³⁵ waist to height ratio,^{136, 137} the body shape index (ABSI,^138-140 derived from weight, height, and waist circumference), and anthropometric risk index (ARI,¹⁴¹ derived from height, BMI, and ABSI). Waist circumference, which can be measured in clinical settings with a flexible tape placed on a horizontal plane at the level of the iliac crest as seen from the anterior view, is used most frequently by clinicians and is recommended for inclusion as part of the routine obesity evaluation by several organizations.^{3, 142-144}

Elevated waist circumference has been associated with increased mortality, CVD, and diabetes risk independent of BMI, and combining waist circumference with BMI may more accurately assess obesity-related mortality and morbidity risk.^{3, 134, 145, 146} The waist circumference cut-points in current use were recommended by the 1998 National Heart, Lung, and Blood Institute (NHLBI) obesity education initiative expert panel, which recommended that waist circumference be considered elevated when greater or equal to 40 inches (102 cm) for men and 35 inches (88 cm) for women.¹⁴⁷ A 2008 WHO Expert Consultation concluded that these levels were associated with substantially increased risk and recommended using lower cut-points (>94 cm in men, >80 cm in women) to identify increased risk.¹⁴⁸ The International Diabetes Federation suggested different cut-points for South Asians, Chinese, and Japanese individuals (>90 cm in men, >80 cm in women).^{149, 150} A 2013 AHA/ACC/TOS panel was unable to formulate an evidence statement on specific waist circumference cut-points and recommended continuing with current cut-points until further evidence became available.³

Waist circumference measurements may be particularly useful among certain subgroups (Appendix A). For example, because of fat redistribution with aging, waist circumference may be more closely associated with morbidity and mortality in elderly populations.⁸⁵ In a pooled analysis of over 58,000 persons ages 65 to 74 years, the relative risk of mortality in older persons with a healthy weight and a large waist circumference was generally higher than for those with overweight and a small waist circumference.¹⁵¹ Evidence about whether waist circumference can improve the predictive ability of obesity screening for health outcomes in nonwhite groups is mixed.^{15, 28, 131, 152-155}

Treatment

Clinical interventions to achieve and maintain weight reduction include behavior-based interventions to induce lifestyle change (i.e., dietary restriction, increased physical activity, and decreasing sedentary lifestyle), pharmacotherapy, and surgery. Behavior-based clinical interventions optimally will combine information on safe physical activity and healthy eating for weight loss with cognitive and behavior-based management techniques to help participants make and maintain lifestyle changes.¹⁵⁶ Interventions often include behavior change techniques such as facilitating goal setting, prompting self-monitoring, weighing pros and cons, drawing the health benefit link, and encouraging social support and can be provided through individual counseling sessions (in-person or remotely), group counseling sessions, technology-based modalities such as computer-based modules, computer- and smartphone-based applications, and text messages, print materials or combinations of these formats.

Several medications are currently approved in the United States for the management of obesity, including weight loss and maintenance of weight loss, in conjunction with a reduced calorie diet. The U.S. Food and Drug Administration (FDA) considers a drug is be effective for the treatment of obesity if either of the following two criteria are satisfied: 1) mean weight loss is at least 5 percent greater than control groups, or 2) proportion of subjects who lose at least 5 percent of baseline body weight is at least 35 percent and approximately double the proportion of the control group.¹⁵⁷ Even if these conditions are met, however, a drug might not be approved because the potential risks or harms of the drug outweigh its benefits or efficacy. Weight loss medications are recommended for patients with obesity with an initial BMI greater than or equal to 30 kg/m² or greater than or equal to 27 kg/m² in the presence of other risk factors (e.g., diabetes, dyslipidemia, controlled hypertension). An Endocrine Society clinical practice guideline states that medication should be discontinued if weight loss is less than 5 percent of body weight within the first 3 months.¹⁵⁸

Orlistat has been approved by the FDA as a chronic weight loss medication since 1999.¹⁵⁹ It blocks absorption of 25 to 30 percent of fat calories by inhibiting pancreatic lipases. Ingested fat is not completely hydrolyzed, resulting in increased fecal fat excretion.^{160, 161} The recommended prescription dose is one 120 mg capsule three times a day (TID) with each main meal containing fat. A lower dose of 60 mg TID is available as an over-the-counter medication.¹⁶² The predominant side effects are gastrointestinal, and there may be decreased absorption of some vitamins. Severe liver injury and oxalate-induced kidney injury have been reported rarely in orlistat users.^{160, 161}

Other weight loss medications target appetite mechanisms, primarily working in the arcuate nucleus to stimulate the pro-opiomelanocortin (POMC) neurons, thereby promoting satiety.¹⁵⁸ One such class of drugs, sympathomimetic drugs (e.g., phentermine, diethylproprion), has been approved since the 1960s for short-term use (up to 12 weeks). They block the reuptake of norepinephrine and serotonin into nerve terminals, thereby leading to early satiety and reduced food intake. Because they are only indicated for short-term use, use of these drugs alone in obesity treatment is not included as part of this systematic evidence review.¹⁵⁸

One of these short-acting sympathomimetic drugs, phentermine, was combined with topiramate, and this drug, phentermine-topiramate extended release (phentermine-topiramate, hereafter), was approved in 2012 for chronic weight management.^{163, 164} Topiramate, a GABA receptor modulator, used to treat epilepsy and migraines, was noted to be associated with weight loss in clinical trials, prompting its evaluation as an antiobesity agent.^165-168 The main side effects of this combination drug include insomnia, dry mouth, constipation, paresthesia, dizziness, distortion of taste, elevation of heart rate, psychiatric events (e.g., depression, anxiety), and cognitive changes (e.g., disturbed memory and attention).^{158, 169} The FDA required a postmarketing prospective cohort and drug use study evaluating oral cleft risks, a randomized, controlled trial (RCT) evaluating renal function in adults with obesity, and an RCT to examine effects on the incidence of major adverse CVD events in subjects with CVD.¹⁶⁴

Another drug, lorcaserin hydrochloride (lorcaserin, hereafter), a selective serotonin type 2c receptor agonist, was also approved by the FDA in 2012 for chronic weight management.^{163, 170} Serotonin reduces food intake and thereby body weight.^171-173 Adverse effects of lorcaserin include headache, nausea, dry mouth, constipation, dizziness, fatigue, cough, and nasopharyngitis.^{158, 169, 174} The FDA required a postmarketing randomized, double-blind, placebo-controlled trial to evaluate the effect of long-term treatment on the incidence of major adverse cardiovascular events (including serial echocardiographic assessments) in those with CVD (final submission to FDA due 12/2018). The FDA also required postmarketing reports of cardiac valve disorders, serotonin syndrome, neuroleptic malignant syndrome, mood and cognitive disorders, and benign and malignant neoplasms.¹⁷⁰

The combination of naltrexone hydrochloride and bupropion hydrochloride (naltrexone and bupropion, hereafter) was approved for chronic weight management by the FDA in 2014.¹⁷⁰ Bupropion is a dopamine and norepinephrine reuptake inhibitor approved for the treatment of depression and prevention of weight gain during smoking discontinuation.^{175, 176} Naltrexone is an opioid receptor antagonist. Side effects include nausea, constipation, headache, vomiting, and dizziness.¹⁵⁸ The FDA required a postmarketing cardiovascular outcomes trial designed to rule out a significant increase in CVD risk. In addition to the unknown CVD risks, the following were also noted during the FDA approval process: seizures (known risk with bupropion), cognitive effects (mostly attention), renal function (creatinine increase), and liver harms (known risk with naltrexone).¹⁷⁰

Liraglutide was approved as a chronic weight management drug in 2014.¹⁷⁷ Liraglutide is a long-acting glucagon-like polypeptide-1 (GLP-1) analog also used for treating diabetes. GLP-1 is a gastrointestinal peptide that stimulates glucose-dependent insulin secretion and inhibits glucagon release and gastric emptying. GLP-1 agonists also affect the POMC neurons and cause satiety.¹⁷⁸ For weight management, it is given a dose of 3 mg daily, which is higher than the dose used for treating diabetes (1.8 mg daily). Side effects include nausea, vomiting, and pancreatitis. A Risk Evaluation and Mitigation Strategies (REMS) requirement was made for physician education regarding the risk of medullary thyroid carcinoma (black box warning) and acute pancreatitis. There was also the requirement of a medullary thyroid cancer registry (15 years) and reanalysis of CVD outcomes trials to examine breast cancer risk. There is also an ongoing postmarketing study of diabetes level dosage and the risk of CVD, medullary thyroid carcinoma, pancreatitis, renal safety, hypoglycemia, immunological reactions, gallbladder disease, and neoplasms in type 2 diabetes mellitus.¹⁷⁷

Bariatric surgery, the most effective weight loss treatment,¹⁷⁹ is one of the fastest growing operative procedures performed worldwide (estimated >340,000 operations in 2011).¹⁸⁰ Bariatric surgical procedures result in weight loss through two mechanisms. Some procedures cause malabsorption by shortening the length of the functional small intestine, either through bypass of the absorptive surface area or diversion of the biliopancreatic secretions that facilitate absorption (e.g., biliopancreatic diversion with duodenal switch). Other procedures cause restriction and limit caloric intake by reducing the stomach’s reservoir capacity via resection, bypass, or creation of a proximal gastric outlet (e.g., laparoscopic adjustable gastric band, sleeve gastrectomy). Some procedures have both a restrictive and malabsorptive component (e.g., Roux-en-Y gastric bypass). There is growing evidence that bariatric surgical procedures also result in weight loss through neurohormonal effects on the regulation of energy balance.¹⁸¹

Current Clinical Practice

Expert organizations generally agree that all adults should be screened for overweight and obesity using at least BMI (Table 1).^{143, 144, 156, 182} Measuring weight at periodic health examinations is now part of standard clinical practice in most medical settings. Despite these guidelines and the ease of determining BMI, surveys have indicated that fewer than one-half of patients with BMIs greater than 30 kg/m² are documented as having obesity in the medical record,^{183, 184} and less than one-quarter of providers state that they consistently and systematically track patients over time with regard to their weight.¹⁸⁵

Table 1

Recent Guidelines on the Assessment of Overweight and Obesity in Adults.

Because central adiposity is emerging as a useful risk factor, several organizations also recommend measuring waist circumference as part of screening (Table 1).^{142-144, 156} For waist circumference, the NHLBI (in collaboration with the AHA, ACC, and TOS) and WHO have defined cut-points for abdominal obesity as greater than 88 cm for women and greater than 102 cm for men.¹⁵⁶ In Asians, the WHO has suggested that countries consider lower cut-points: greater than 80 cm in women and greater than 90 cm in men.^{1, 186}

Experts recommend that persons with obesity be given advice about diet, exercise, and lifestyle management.^{3, 142, 144, 158, 182} In 2011, Medicare began reimbursing for behavior-based weight loss treatment for beneficiaries with obesity (BMI ≥30 kg/m²). The new payment allows up to 20 weight loss-related visits with primary care physicians, nurse practitioners, physician assistants, or clinical nurse specialists. In a serial cross-sectional analysis of fee-for-service Medicare claims, a very small proportion of persons with obesity (0.35% and 0.60% in 2012 and 2013) were using the Medicare Obesity Benefit, with only a mean of about 2 claims per user.¹¹⁵ Under the Affordable Care Act, there is no exact definition of what obesity counseling must include, and coverage varies from plan to plan.¹⁸⁷ But most health insurance plans, including all plans purchased through the Marketplace, offer coverage for obesity screening and counseling. However, primary care–delivered, weight-related counseling rates remain low. In one recent analysis, only 30 percent of patients with obesity received weight counseling in 2007–2008 (compared with 40% in 1995–1996).¹⁸⁸ These data are consistent with other surveys, which show that 35 to 60 percent of providers provide specific guidance on diet, physical activity, or weight control to their patients who have obesity.^{183, 189-192} In a recent survey, almost all (97%) physicians felt responsible for promoting weight-related care. However, there was little familiarity with select obesity guidelines.¹⁸⁵ In addition, more than half of the physicians had concerns about the effectiveness of weight loss interventions, and nearly two-thirds felt they lacked effective strategies to help patients.¹⁸⁴ In contrast, nutrition professionals self-identify as being the most qualified group to help patients lose weight, and those who report receiving high-quality training in weight loss counseling report high degrees of confidence and success in helping patients with obesity to lose weight.¹⁹³

Several organizations and expert panels recommend weight loss medications for those with BMIs of 30 kg/m² or over (or 27 kg/m² with comorbidities) who are unsuccessful with lifestyle changes.^{143, 144, 156, 158} However, in a recent survey, there was little consensus among physicians about when to initiate weight loss medications, and physicians expected more weight loss with medications than is realistic.¹⁸⁵ Many adults who are prescribed weight loss medications may not meet approved indications and/or may have contraindications.¹⁹⁴ An analysis of pharmacy claims data from 2012 to 2015 found that the adoption of new antiobesity medications has remained level, while the adoption of new antidiabetes medications (subtype 2 sodium-glucose transport protein inhibitors) has increased nearly exponentially.¹⁹⁵

Previous USPSTF Recommendation

In 2012, the USPSTF recommended screening all adults for obesity and referral of patients with BMIs of 30 kg/m² or higher to intensive, multicomponent behavioral interventions (B recommendation).¹⁹⁶