Obesity refers to having an excess amount of body fat in relation to lean body mass, or a body mass index (BMI) of ≥30 kg/m². Overweight is defined as BMI of 25 to 29.9 kg/m², and morbid obesity refers to adults with a BMI ≥40 kg/m². BMI is used as a surrogate measure of obesity. Weight classification by BMI is summarized in Table 1. Abdominal obesity is defined as waist circumference >102 cm (40 in) in men and >88 cm (35 in) in women.

• The World Health Organization first recognized obesity as a worldwide epidemic in 1997. As of 2005, 1.6 billion adults worldwide were classified as overweight, 400 million of whom were obese. It is predicted that the combination of overweight and obesity will soon eclipse public health issues such as malnutrition and infectious diseases as the most significant cause of poor health.
• Worldwide, data from the Global Burden of Disease Study from 1980 to 2013 indicate the prevalence of adult obesity has increased from 28.8% to 36.9% in men and 29.8% to 38% in women. The prevalence of childhood and adolescent obesity has also substantially increased.
• Based on U.S. NHANES data from 2011 to 2012, the prevalence of abdominal obesity was 54%. It is estimated that by 2023, 2 in every 5 adults and 1 in every 4 children in the U.S. will be categorized as obese.
• Obesity is the most common health problem in women of reproductive age. Obesity before pregnancy is disproportionately prevalent among women who identify as American Indian and Alaska Native (40%), non-Hispanic Black (39%), or Hispanic (32%), as compared with those who identify as non-Hispanic White (26%) or non-Hispanic Asian (10%).¹
• The present cost of obesity in the U.S. population is estimated at $100 billion annually. Approximately two thirds of people living in the U.S. are overweight, which is the highest percentage in the world.
• For persons with a BMI ≥30 kg/m², all-cause mortality is increased by 50% to 100% above that of persons with BMI in the range of 20 to 25 kg/m².
• Obesity is an independent risk factor for cardiovascular disease (CVD), type 2 diabetes, hypertension, cancer (particularly colon, prostate, breast, and gynecologic malignancies), sleep apnea, degenerative joint disease, thromboembolic disorders, digestive tract diseases (gallstones), and dermatologic disorders.
• Significant morbidity and risk of death are projected to begin in young adulthood, resulting in >100,000 excess cases of coronary heart disease (CHD) by 2035, even with the most modest projection of future obesity.
• When children enter kindergarten, 12.4% are obese, and another 14.9% are overweight. Data show that incident obesity between the ages of 5 and 14 yr is more likely to have occurred at younger ages.²
• Obesity in adolescence is significantly associated with increased risk of incident severe obesity in adulthood, with variations by sex and race/ethnicity. Overweight or obese adults who were obese as children have increased risk of type 2 DM, dyslipidemia, hypertension, and carotid artery atherosclerosis.
• Obesity is a major preventable cause of death and disability in the U.S. (the other is tobacco).
• Extensive data indicate that weight loss can reverse or arrest the harmful effects of obesity.
• In 2013 nearly 180,000 bariatric surgery procedures were performed in the U.S. Of these procedures 42% were laparoscopic sleeve gastrectomy, 34% were Roux-en-Y gastric bypass, and 15% were laparoscopic adjustable gastric banding.

• Physical examination should assess the degree and distribution of body fat, signs of secondary causes of obesity, and obesity-related comorbidities.
• Increased waist circumference is apparent. Excess abdominal fat is clinically defined as a waist circumference >40 in (>102 cm) in men and >35 in (>88 cm) in women (in Asian men and women, >36 in and >33 in, respectively). Central obesity is a risk factor for mortality even among individuals with normal BMIs.
• Symptoms associated with hypertension, coronary artery disease (CAD), and diabetes (e.g., polyuria, polydipsia, acanthosis nigricans, retinopathy, and neuropathy) may be present.
• Obesity is associated with cardiac hypertrophy, diastolic dysfunction, and decreased aortic compliance, which are independent predictors of cardiovascular risk.
• Joint pain and swelling are associated with degenerative joint disease secondary to obesity.
• The physical exam and ECG often underestimate the presence and extent of cardiac dysfunction in obese patients. Jugular venous distention and hepatojugular reflux may not be seen, and heart sounds are frequently distant.
• A large quantity of fluid is present in the interstitial space of adipose tissue, as the interstitial space is ∼10% of the tissue wet weight. This excess fluid in this compartment, if redistributed into the circulation, can have negative repercussions in obese individuals with heart failure. Obese individuals have higher cardiac output and a lower total peripheral resistance than do lean individuals, and obesity is associated with persistence of elevated cardiac filling pressure during exercise.
• Obesity predisposes to heart failure through several different mechanisms: Increased total blood volume, increased cardiac output, left ventricular hypertrophy (LVH), left ventricular diastolic dysfunction, and adipositas cordis (excessive epicardial fat and fatty infiltration of the myocardium).

• The pathophysiology of obesity is complex and poorly understood, but includes social, nutritional, physiologic, psychological, and genetic factors (Table 2).
• Environmental factors such as a sedentary lifestyle and chronic ingestion of excess calories can cause obesity.
• Obesity may be related to genetic factors, which are thought to be polygenic. Genetic studies with adopted children have demonstrated that they have similar BMIs to their biologic parents but not their adoptive parents. Twin studies also demonstrate a genetic influence on BMI.
• Secondary causes of obesity can result from medications (antipsychotics, steroids, and protease inhibitors being common ones) and neuroendocrine disorders (like Cushing syndrome and hypothyroidism).
• Box 1 summarizes medical conditions associated with severe obesity.

It is important to evaluate obese patients for secondary medical causes of obesity. Hypothalamic disorders, hypothyroidism, Cushing syndrome, insulinoma, depression, and drugs (corticosteroids, antidepressants, second-generation antipsychotics, sulfonylureas, and HIV protease inhibitors) can cause obesity. In children, certain genetic conditions, such as Prader-Willi syndrome, are associated with obesity.

History should be obtained regarding weight change, family history of obesity, and eating and exercise behavior. Assessment for eating disorders and depression should be made. Attention should be directed to the use of nutritional supplements, over-the-counter medications, hormones, diuretics, and laxatives. The workup of an obese patient typically requires laboratory work to assess for risks and complications as well as to rule out underlying causative medical conditions.

• Obese patients should be assessed for medical consequences of their obesity by screening for metabolic syndrome. This includes measurement of fasting lipid profile, blood pressure, and waist circumference and screening for diabetes or prediabetes (oral glucose tolerance test, fasting glucose, or hemoglobin A1C).
• Polycythemia might warrant screening for sleep apnea. Liver function tests should be obtained to screen for hepatic steatosis.
• In the proper clinical setting, thyroid function studies and dexamethasone suppression testing will exclude hypothyroidism and Cushing syndrome as underlying causes of obesity. If insulinoma is suspected, the patient will need to undergo a 72-hr fast to confirm hypoglycemia with inappropriate insulin secretion.
• Obesity is associated with changes in the ECG, including a reduction in voltage and nonspecific ST-T changes that may interfere with diagnosis of LVH or CAD.

• Several methods are available for determining or calculating total body fat but offer no significant advantage over the BMI. These include measurement of total body water, total body potassium, bioelectrical impedance, and dual-energy x-ray absorptiometry.
• Buoyancy testing is an accurate method for determining total body fat composition.

Obesity increases the risk of obstructive sleep apnea, which, in turn, increases the risks of hypertension, cardiac arrhythmias, CVD, stroke, and heart failure. Therefore one should have a low threshold to screen obese patients for obstructive sleep apnea via sleep study/polysomnography.

• The cornerstones for weight management and reduction are calorie restriction, exercise, and behavioral modification. Assessment of patient’s willingness to make changes must be evaluated, as treatment is more likely to succeed in motivated patients.
• The NHLBI guidelines recommend an initial diet to produce a calorie deficit of 500 to 1000 kcal/day. This has been shown to reduce total body weight by an average of 8% over 3 to 12 mo.
• These guidelines recommend the use of a food diary to focus on dietary substitutes.
• Thirty min of moderate-intensity activity on 5 or more days of the wk results in health benefits for obese individuals. Moreover, several studies indicate that 60 to 80 min of moderate to vigorous physical activity may provide additional benefit.
• Increased physical activity without caloric restriction (minimal or no weight loss) can reduce abdominal (visceral) adipose tissue and improve insulin resistance.
• The key features of the standard behavioral modification program include goal setting, self-monitoring, stimulus control (modification of one’s environment to enhance behaviors that will support weight management), cognitive restructuring (increased awareness of perceptions of oneself and one’s weight), and prevention of relapse (weight regain).
• Mammalian sleep is closely integrated with the regulation of energy balance. Trials have shown that the amount of human sleep contributes to the maintenance of fat-free body mass at times of decreased energy intake. Lack of sufficient sleep may compromise the efficacy of typical dietary interventions for weight loss and related metabolic risk reduction.

• According to the NHLBI Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults and the U.S. Food and Drug Administration (FDA), pharmacotherapy is indicated for:
  1. Obese patients with a BMI ≥30
  2. Overweight patients with a BMI of ≥27 and concomitant obesity-related risk factors or diseases, such as hypertension, diabetes, or dyslipidemia
• Pharmacologic treatment options include:
  1. Gastrointestinal lipase inhibitors: Orlistat is the only drug available for long-term treatment of obesity. It blocks the digestion and absorption of ingested dietary fat. It is a reversible inhibitor of pancreatic, gastric, and carboxyl ester lipases and phospholipase A2, which are required for the hydrolysis of dietary fat in the gastrointestinal tract. Side effects include flatulence, fecal incontinence, cramps, and oily spotting. There can also be impairment of absorption of fat-soluble vitamins (A, D, E, K) and beta-carotene. Oxalate-associated acute kidney injury and rare severe liver injury have also been reported.
  2. C serotonin agonists: Lorcaserin is a selective serotonin agonist that acts centrally to reduce appetite, aiding weight loss. Adverse effects include headache, upper respiratory infections, dizziness, and nausea. While there is little evidence of serotonin-associated cardiac valvular disease or pulmonary hypertension (as seen with nonselective serotonergic agonists fenfluramine and dexfenfluramine), long-term data is currently limited.
  3. Sympathomimetic medications: Phentermine and diethylpropion are currently approved for short-term treatment of obesity. They reduce food intake by causing early satiety. Side effects include increased blood pressure and increased pulse. They are Schedule IV drugs with a potential for abuse. Other sympathomimetic drugs that have been removed from the market due to concerns about cardiovascular safety are sibutramine, phenylpropanolamine, and ephedrine.
  4. Antidepressants: While not FDA-approved for treatment of obesity alone, bupropion and fluoxetine are antidepressants that have been associated with modest weight loss. The FDA has recently approved a fixed-dose combination of bupropion with the opioid receptor antagonist naltrexone. It is called Contrave and approved for use as an adjunct to diet and exercise in patients with BMI ≥30 kg/m² or a BMI ≥27 kg/m² and one or more weight-related comorbidities (e.g., diabetes, hypertension, dyslipidemia).
  5. Antiepileptic drugs: Zonisamide and topiramate (also used in migraine therapy) have been associated with weight loss in clinical trials but are not currently FDA-approved for treatment of obesity alone.
  6. Diabetes drugs: While not FDA-approved for treatment of obesity alone, metformin and pramlintide (synthetic human amylin) have been associated with weight loss in the treatment of individuals with diabetes. The GLP-1 receptor agonist liraglutide (Victoza) is now FDA approved at a higher dose as Saxenda for chronic weight management in adults with BMI ≥30 or a BMI ≥27 with a weight-related comorbidity such as hypertension, dyslipidemia, or diabetes. Semaglutide (Ozempic, Rybelsus) plus lifestyle intervention is associated with clinically relevant reduction in body weight in adults with overweight or obesity.³ In adolescents with obesity, a trial of once-weekly semaglutide plus lifestyle intervention resulted in a mean change in BMI of 16.1% with semaglutide vs. 0.6% with placebo after 68 weeks.^3a

• According to the NHLBI guidelines, surgical intervention is an option for selected patients with clinically severe obesity (a BMI ≥40 or a BMI ≥35 with comorbid conditions), when patients are at high risk for obesity-associated morbidity or death, and when less invasive methods of weight loss have failed. Box 2 summarizes patient requirements for bariatric surgery. Preoperative evaluation and postoperative care are described in Box 3
• Eligible patients should also be at an acceptable risk for surgery, well informed, and motivated.
• Restrictive surgeries limit the amount of food the stomach can hold and slow the rate of gastric emptying. These include Roux-en-Y gastric bypass (RYGB), vertical banded gastroplasty (VSG), laparoscopic adjustable silicone gastric banding (LAGB), and endoscopic sleeve gastroplasty (ESG). RYGB combines creation of a small gastric pouch with a modest intestinal or small bowel bypass to produce weight loss through both restrictive and malabsorptive means. A traditional RYGB consists of transection of a small (15-ml) proximal gastric pouch along the lesser curvature of the stomach from the larger gastric segment, combined with a modest (encompassing 60 to 150 cm) intestinal bypass. The Roux-en-Y configuration allows biliopancreatic secretions and digestive juices to pass through the bile duct into the duodenum and then merge with the alimentary stream passing down from the stomach at the Y-type connection. The lengths of both the Roux and biliopancreatic limbs can be varied to produce more malabsorption. Most weight is lost in the first year. Approximately 80% of patients typically experience weight stabilization, usually slightly above weight nadir, approximately 3 yr after surgery. The remaining 20% of patients slowly regain excess weight over longer-term follow-up and risk regaining much of the lost weight. VSG (Fig. E1) is now the most commonly performed major bariatric procedure. This operation restricts intake via a 70% vertical gastric resection, creating a long and narrow tubular gastric reservoir with no intestinal bypass. LAGB is an inflatable silicone prosthetic device that is placed around the top portion of the stomach, just below the esophagus (Fig. E2) and restricts the upper stomach size to a small volume. The band is attached to a reservoir, with a port placed under the skin on the abdominal wall, and the inner lining of the band is a balloon that is adjustable by the addition or removal of saline from the reservoir port. Inflation of the band increases the restriction of gastric outlet size and food flow. Band slippage is the most common LAGB complication. Other potential complications include port or tubing malfunction, stomal obstruction, band erosion, pouch dilation, and port infection. Gastric necrosis of the stomach wall is a rarer late complication that results from ischemia caused by a combination of gastric prolapse-the part of the stomach below the band herniates up through the device-and pressure from the band. Less commonly used are biliopancreatic diversion (BPD) and BPD with duodenal switch (BPDDS) procedures (Fig. E3), which result in an extreme degree of malabsorption and are reserved for the treatment of “superobese” patients. BPD combines a partial, subtotal gastrectomy and a very long Roux-en-Y anastomosis with a short common channel for nutrient absorption. With this procedure, patients can eat much larger quantities of food and still achieve and maintain weight loss. Disadvantages include higher postoperative surgical risks, loose and foul-smelling stools, intestinal ulcers, anemia, vitamin and mineral deficiencies, and possible protein-calorie malnutrition. Because of these potential problems, patients who undergo BPD require lifelong dietary supplementation and close follow-up monitoring.⁴ ESG is a relatively new procedure. Larger trials will determine its long-term efficacy and safety.⁵ In ESG the endoscopist places transmural gastric sutures to restrict gastric volume and delay gastric emptying. This endoscopic procedure is reversible and avoids complications associated with more invasive procedures. Complications of bariatric surgery are summarized in Box E4.
• Gastric bypass has better outcomes than gastric band procedures for long-term weight loss, type 2 diabetes control and remission, hypertension, and hyperlipidemia.⁶ These procedures have benefits that include lower perioperative mortality rate, a quicker recovery period, and no malabsorption issues. However, they are not as effective as gastric bypass for weight reduction and comorbidity improvement.
  1. Malabsorptive surgeries reduce nutrient absorption by shortening the length of small intestine. These include jejunoileal bypass and the duodenal switch operation (DS).
  2. Restrictive malabsorptive bypass procedures combine the elements of gastric restriction and selective malabsorption. These include Roux-en-Y gastric bypass (considered the gold standard because of its high level of effectiveness and durability) and biliopancreatic diversion. These procedures have higher rates of comorbidity improvement than restrictive surgeries but can be complicated by malabsorption and nutritional deficiencies.
• Compared with usual care, bariatric surgery is associated with reduced number of cardiovascular deaths and lower incidence of cardiovascular events and cancer mortality⁷ in obese adults. A study on bariatric surgery patients demonstrated a significant reduction in long-term cardiovascular events. Ten-yr follow-up estimated relative risk reductions ranging from 18% to 79% according to the Framingham risk score, and 8% to 62% with the PROCAM risk score.
• A long-term observational study of obese patients with type 2 diabetes showed that bariatric surgery was associated with higher diabetes remission rates and fewer complications than usual care. Remission of type 2 DM occurs in 60% to 80% of patients 2 yr after surgery and persists in about 30% of patients 15 yr after Roux-en-Y gastric bypass.
• Liposuction is removal of fat by aspiration after injection of physiologic saline. This technique reduces the subcutaneous fat but has failed to improve insulin sensitivity or risk factors for CHD.
• Fluid filled, space-occupying intragastric balloons (IGBs) can also be used for weight loss. They are inserted endoscopically and left in place for 6 months. Volume can be adjusted endoscopically. Weight loss is as much as 10% of body weight. Weight gain after removal is an issue as only 74% of IGB patients were able to maintain more than 40% of weight loss during treatment in a recent study.⁸
• The Maestro Rechargeable System is a subcutaneously implanted device FDA approved for weight loss in adults with a BMI of 40 to 45 or with a BMI of ≥35 and at least one obesity-related comorbidity. It utilizes high-frequency electrical pulses to block vagus nerve signals between the brain and stomach. It is less effective than bariatric surgery for weight loss. The list price for the Maestro system exceeds $15,000.
• The AspireAssist device is FDA approved for weight loss in adults ≥22 yr old with a BMI of 35 to 55. It requires the insertion of a PEG tube endoscopically and pulled through a percutaneous incision. Thirty min after a meal, the patient attaches a connector to it and drains a portion of their stomach content into a toilet. The tube is then flushed with potable water. The connector stops working after 115 cycles (6 wk) and is replaced at a follow-up appointment. Estimated cost for procedure and follow-ups are $13,000 for the first yr.
• Plenity is a hydrogel formulation of cellulose and citric acid available in capsules taken 20 to 30 min before lunch or dinner with 500 ml of water. The hydrogel particles hydrate up to 100 times their original weight in the stomach to create a feeling of fullness. The matrix is then digested and broken down in the colon and eliminated in the feces. Plenity is available by prescription for patients with a BMI of 25 to 30 kg/m² regardless of comorbidities.

• The incidence of venous thromboembolism in the upper tertile of BMI was 2.42 times that of the lowest BMI tertile. Obese patients have a higher incidence of postoperative thromboembolic events when undergoing noncardiac surgery.
• Obesity may be associated with higher rates of postoperative pulmonary complications and poor wound healing.
• Weight-stable obese subjects have an increased risk of arrhythmias and sudden death even in the absence of cardiac dysfunction.
• Obesity and the cardiac autonomic nervous system are intrinsically related. A 10% increase in body weight is associated with a decline in parasympathetic tone accompanied by a rise in mean heart rate. Conversely, a 10% weight loss in severely obese patients is associated with significant improvement in autonomic nervous system cardiac modulation, including decreased heart rate and increased heart rate variability.
• Postmortem Determinants of Atherosclerosis in Youth (PDAY) study data provided convincing evidence that obesity in adolescents and young adults accelerates the progression of atherosclerosis decades before the appearance of clinical manifestations.
• Obesity accelerates the progression of native coronary atherosclerosis and after coronary artery bypass grafting.
• In older adults, obesity is associated with protection against hip fracture, but this protective effect on bone status does not offset the extensive array of potential adverse effects on conditions common in the older population.
• A 3-yr trial comparing midterm effects of bariatric surgery on patients with obesity and hypertension revealed Roux-en-Y gastric bypass (RYGB) is an effective strategy for midterm blood pressure control and hypertension remission, with fewer medications required in patients with hypertension and obesity.⁸
• A study on the effects of diet vs. gastric bypass on metabolic function in type 2 diabetes revealed that the metabolic benefits of gastric bypass surgery and diet are similar and related to weight loss itself, with no evident clinically important effects independent of weight loss.⁹ A 10-yr trial in obese diabetic patients comparing bariatric surgery versus medical treatment for promoting remission and preventing diabetes-related complications revealed that surgery patients had fewer diabetes-related complications but more digestive and metabolic complications.^9,10

Obesity is commonly seen in the primary care setting. If pharmacologic therapy is considered, consultation with physicians specializing in obesity and experienced with the use of the drug is recommended. In addition, consultation with nutritionists and behavioral therapists is helpful. A consultation with general surgery is indicated in patients being considered for surgical intervention.

• Enhanced weight-loss counseling helps about one third of obese patients achieve long-term, clinically meaningful weight loss. Adults can lose 1 to 2 lbs (0.45 to 0.9 kg) per wk by consuming 500 to 1000 fewer calories per day.
• The NHLBI launched the Obesity Education Initiative in January 1991. The overall purpose of the initiative is to help reduce the prevalence of overweight along with the prevalence of physical inactivity to reduce the risk of CHD and overall morbidity and mortality rates from CHD.
• Brown adipose tissue represents a natural target for the modulation of energy expenditure. The presence of brown adipose tissue in humans may be quantified with the use of 18F-fluorodeoxyglucose PET-computed tomography (CT). The amount of brown adipose tissue is inversely correlated with BMI, suggesting a potential role of brown adipose tissue in adult human metabolism.
• Obesity, glucose intolerance, and hypertension in childhood are strongly associated with increased rates of premature death from endogenous causes in this population.
• Recent trials have shown that among persons living in a controlled setting, calories alone account for the increase in fat. Protein affected energy expenditure and storage of lean body mass but not body fat storage.
• Data are lacking for the role of pharmacotherapy and bariatric surgery in the elderly population.

• Prevention of overweight and obesity involves both increasing physical activity and dietary modification to reduce caloric intake.
• There is compelling evidence that prevention of weight regain in formerly obese individuals requires 60 to 90 min of moderate-intensity activity or lesser amounts of vigorous intensity activity.
• Moderate-intensity activity of approximately 45 to 60 min per day, or 1.7 physical activity level (PAL), is required to prevent the transition to overweight or obesity. For children, even more activity time is recommended.
• Clinicians can help guide patients to develop personalized eating plans and help them recognize the contributions of fat, concentrated carbohydrates, and large portion sizes.
• Clinicians must work with patients to modify other risk factors such as tobacco use, high glycemic intake, and elevated blood pressure to prevent the long-term chronic disease sequelae of obesity. Generally lower carbohydrate, moderate fat intake, with stable protein and energy intake results in higher energy expenditure during weight-loss maintenance.⁶
• Regular screening of body weight and BMI measurements at routine office visits can help identify early weight gain.
• Among obese adolescents, the most rapid weight gain occurs between 2 and 6 yr of age. Most children who are obese at that age are obese in adolescence.⁶
• A clinical practice guideline for the evaluation from the American Academy of Pediatrics¹¹ for evaluating and managing children and adolescents with obesity recommends the following:
  1. Any child ≥2 yr old with BMI ≥85th percentile should undergo a comprehensive history and physical, including examinations of mental-behavioral health, social determinants of health, blood pressure, and age-appropriate blood work (e.g., lipids, ALT, HbA1c).
  2. The mainstay of management is intensive health behavior and lifestyle treatment (IHBLT), an in-person, family-based program requiring at least 26 hours of face-to-face time during 3 to 12 months.
  3. Pharmacotherapy can be used as an adjunct to IHBLT for selected teens ≥12 yr old. Medications (metformin, orlistat, glucagon-like peptide-1 receptor agonists, topiramate) should be chosen based on indications, benefits, and risks.
  4. Evaluation for metabolic and bariatric surgery should be considered for teens ≥13 yr old with severe obesity (BMI ≥120% of the 95th percentile) and clinically significant co-morbidities.

Information can be obtained on the American Obesity Association website (http://www.obesity.org/) and the American Medical Association website (https://www.ama-assn.org/).

Obesity, Female (Patient Information)

Obesity, Male (Patient Information)

Obesity, Child (Patient Information)