The definition of obesity has been evolving over the past few decades. Historically, obesity has been defined simply as an excess of body fat [9]. Today, however, measurement of body weight and height is most often utilized as a measure of obesity.

Initially, weight-for-height tables were used to determine the normal weight range for a given height. These tables were replaced with other indices when they were found to be of limited value due to their general estimates of frame size and bias toward the White population [10]. These tables were replaced with the body mass index (BMI), which is calculated by weight in kg/height in meters² or [weight (lbs)/height (inches)²] x 703. For most individuals, BMI correlates well with the proportion of body fat.

BMI is considered the general standard for defining obesity (Figure 1). An online BMI calculator is available at https://www.nhlbi.nih.gov/health/educational/lose_wt/BMI/bmicalc.htm.

These definitions are based on epidemiologic evidence that suggests health risks are greater at or above a BMI of 25, compared to those below 25. The risk of death from all causes rises with increasing BMI, with a significant increase at BMI greater than 30. In a large cohort study published in the New England Journal of Medicine in 2006, persons with a BMI greater than 30 had mortality rates two to three times that of persons with BMI between 20 and 25 [12].

In defining obesity, NIH also identified excess fat in the abdomen out of proportion to total body fat as an independent predictor of risk factors and morbidity [11]. The gender-specific cutoffs for waist circumference are as follows:

These are of value only for those with a BMI between 25.5 and 34.9. It is not useful to measure waist circumference in individuals with BMI >35, as such patients are already at increased risk.

Since 1960, the prevalence of obesity in the United States has been on an upward trajectory, with rates increasing dramatically in the past few decades. In 1980, the percentage of obese and extremely obese adults was 15% and 1.4% of the total population, respectively; by 1994, the numbers had increased to 23.2% and 3.0% [1]. In the year 2000, 30.9% of the adult population was obese and 5.0% were extremely obese [1]. Data collected in 2017–2020 show that 41.9% are obese and 9.2% are extremely obese (class III); an additional 31.9% of adults are overweight [1,75]. That means that more than 83% of Americans 20 years of age or older are above a healthy weight and are at an increased risk for disease and early death.

With race/ethnic origin not factored, the prevalences of overweight and obesity are higher for men (38.2% and 43.0%) than for women (25.8% and 41.9%), but rate of extreme obesity is higher among women [75]. In the overall population, approximately 6.9% of men and 11.5% of women are extremely obese [1,75].

When considered as a single race, the prevalence of obesity is greater among individuals of African (49.9%) and among individuals of Hispanic (45.6%) descent than among adults of European or Caucasian descent (41.4%) [75]. Native American/Alaska Natives and Native Hawaiian/Pacific Islanders have an obesity prevalence of 43.7% and 34.6%, respectively [42,74]. Asian Americans are an exception, with a prevalence of 17.4%, much lower than in the general population. Although the rate of obesity is higher in many American racial/ethnic groups compared with non-Hispanic White population, White individuals make up the majority of cases [75].

Obesity is most common among individuals 40 to 59 years of age, with 44.8% of American men and women in this age group fitting this description [42,75]. However, roughly 57.5% of African American women and 51.1% of Hispanic women in this age group are obese [42,75]. There is also a higher incidence of obesity (greater in women than in men) with lower socioeconomic status among all races [42,74].

Of particular concern is the increase in the number of children who have high BMIs. Presently, nearly 13% of children 2 to 5 years of age, 20.7% of children 6 to 11 years of age, and 22.2% of adolescents between 12 to 19 years of age are obese [14,110]. Hispanics (26.2%) and non-Hispanic Black individuals (24.8%) have a higher prevalence of obesity than non-Hispanic White individuals (16.6%). The prevalence of obesity in adolescents has more than tripled since 1970 [14]. This is especially troubling because overweight adolescents have a 70% chance of becoming overweight or obese adults; if their parents are overweight or obese, this chance increases to 80% [101]. Adolescent obesity is associated with increased risk for cardiovascular disease, type 2 diabetes, and certain malignancies (e.g., leukemia, Hodgkin lymphoma, colorectal cancer, breast cancer) in adulthood [121].

Though the scientific community has been unable to identify a single etiologic agent for obesity, there have been clinical advances in the past two decades. Obesity is known to be associated with certain exogenous causes. Genetic factors gained national attention after the discovery of leptin in 1995 by positional cloning in the leptin-deficient mouse model of obesity [19]. Leptin (derived from the Greek word leptos, meaning "thin") is a 16-kilodalton adipocyte-derived hormone from the ob gene and has been the focus of many genetic investigations to elucidate the pathophysiology of obesity. Though this finding is relatively recent, its existence was suspected twenty years ago. In 1978, Coleman proposed that a circulating factor in the plasma of the db mouse strain, which is both diabetic and obese, could reduce the obesity of the ob mouse (a strain of mice with mutations in leptin) [20]. The db mice were found to have mutations in the leptin receptor and were subsequently resistant to the leptin, unlike the ob mice who possessed a mutated leptin gene but functional leptin receptors. Further investigations revealed that injections of leptin in ob mice could cure obesity and diabetes. After locating the human homologues to the leptin gene and its receptor in 1999, the chromosomal locus containing the leptin gene was determined to be genetically related to human body weight [21]. However, only a few people with mutated leptin genes have been identified, while the majority of obese patients have fully functional leptin genes and receptors.

Genetic diseases with associated obesity include Schinzel syndrome, Bardet-Biedel syndrome, Albright hereditary osteodystrophy, and Prader-Willi syndrome. Many of these genetic disorders present with dysmorphic features, developmental delay, and obesity in addition to changes seen specifically with each disorder [22]. For instance, young males with Prader-Willi syndrome present with the features described above as well as with linear growth defects and undescended testicles.

Overall, the relationship between genetics and obesity cannot be fully determined at this time. Evidence suggests a link between the two, implying that genetics is one of the complex factors involved in the development of this prevalent condition. Although many argue that "obesity genes" cannot be responsible for the epidemic, because the gene pool in the United States had not changed significantly between 1980 and 1994, the etiology of obesity is most likely multifactorial [23]. In 2010, one group of researchers confirmed 14 genetic variations and discovered an additional 18 variations associated with obesity [77]. In 2015, the group published additional research that identified a total of 97 genetic variations [111]. Although the progress with genetic variations related to BMI is promising, further research is needed to clarify the influence of genetics.

Biologic factors must also be considered. Proteins and receptors appear to have a role in weight control. For example, orexin A and B are located in the lateral hypothalamus, an area which may regulate body weight. Ongoing research may help determine the role of orexin in obesity.

Environmental factors seem to play a significant role as well. Data from a longitudinal twin-family study and co-twin control studies combined with population-based data on patterns of dietary intake and physical activity provide some evidence that environment can contribute to obesity [74]. Environmental factors include technologic advances in food processing, marketing, advertising, and behavioral lifestyle. Some theorize that obesity is self-fulfilling in that if an individual is told they are predisposed to becoming fat, he or she will decide there is no point in eating healthy or exercising [78].

Obesity is associated with large number of major medical concerns, such as elevated serum triglycerides (>200 mg/dL), and is a risk factor for many diseases, including [24,80,81,112]:

There is evidence that excess body weight is associated with increased risk for a range of malignancies: endometrial, esophageal, renal, pancreatic, and hepatocellular carcinomas and colorectal, postmenopausal breast, ovarian, gallbladder, and thyroid cancers [123]. In the Nurses' Health Study (a large prospective cohort study involving more than 100,000 women), women older than 35 years with a BMI greater than 27 were found to have an increased risk for cancer, heart disease, and other diseases. For instance, women gaining more than 20 pounds (9 kg) between 18 and 35 years of age doubled their risk for breast cancer compared with women who maintained their weight [25]. Additionally, the age and smoking-adjusted relative risk of non-fatal myocardial infarction and fatal coronary disease for women with BMI 25 to 29 was 1.8; for women with BMI greater than 29, it was 3.3.

Left ventricular hypertrophy (LVH) is often seen in obese patients and correlates to the resulting systemic hypertension [26]. The risk for type 2 diabetes has been reported to be twofold in the mildly obese, fivefold in moderately obese, and tenfold in extremely obese persons [27].

In one study, individuals with a BMI of at least 30 had an elevated risk of pancreatic cancer compared to those with a BMI of less than 23 [28]. A study published in 2012 involving 720,000 men found that overweight adolescents had more than double the risk of developing pancreatic cancer as young or middle-age adults compared to normal weight individuals [79]. In general, obese patients showed an increased risk of 5.4 times that of non-obese patients for endometrial cancer, 3.6 times for gallbladder cancer, 2.4 times for cervical cancer, 1.6 times for ovarian cancer, 1.5 times for breast cancer, 1.7 times for colorectal cancer, and 1.3 times for prostate cancer [29]. Cancer mortality is also increased in obese patients.

The goal of therapy is to reduce body weight as well as body fat and maintain a lower body weight for the long term. The rate of weight loss should be 1 to 2 lbs per week, with a goal of 10% weight loss over six months. Moderate weight loss, defined as 5% to 10% reduction in baseline weight, is associated with clinically meaningful improvement in obesity-related metabolic risk factors and comorbidities, including improved pancreatic beta-cell function, increased sensitivity of liver and skeletal muscle to insulin, and significant reductions in systolic and diastolic blood pressure [126]. It is important to note that weight loss as modest as 10 lbs reduces the risk factors for several diseases. Such weight loss can lower blood pressure, lower blood sugar, reduce inflammation, and improve lipid levels. Unfortunately, most patients believe a weight loss of 30 to 40 lbs is necessary to medically benefit and become discouraged when they do not see such results [31]. Patients should set realistic expectations from the start, with the idea that small losses of 10 lbs can be considered successes. Moreover, physicians must emphasize the importance of long-term weight management and weight loss rather than short-term extreme weight reduction.

Reviewing and modifying diet is one of the most important steps in helping patients lose weight. As a simple rule, caloric intake should be reduced by 500–1,000 calories per day from a patient's current level. Patients with a BMI of 27–35 should reduce total calories by 300–500 daily; patients with BMI greater than 35 should reduce total calories by 500–1,000 daily. This reduction will produce the recommended weight loss of 1 to 2 lbs per week in most patients. The recommended number of total calories will vary depending upon activity level: 1,600 calories for most sedentary women, 2,200 calories for sedentary men or active women, 2,600 calories for active men. To calculate specific caloric requirements, the following approach is useful:

It is important that any diet contain food from all food groups, so that it remains nutritionally adequate. "Fad diets" typically have nutritional deficiencies, and this is one reason why they are potentially dangerous. For example, high-fat, low-carbohydrate diets are low in vitamins E and A, thiamin, folate, calcium, magnesium, and zinc. Low-fat diets are typically deficient in vitamin B12.

The report distinguishes the different types of fat. Saturated fat and trans fatty acids typically raise the amount of LDL in the bloodstream. Because this type of fat has little value, there is no recommended intake requirement, and people should be advised to keep consumption as low as possible. Sources include meat, poultry, baked goods, and dairy products, as well as some vegetable sources, such as coconut and palm oils.

As noted earlier, approximately 26% of American adults rarely (or never) exercise [2]. There are numerous reasons for this, including lack of interest, competing demands for leisure time, lack of knowledge of proper technique, and fear of injury. Compounding this problem, in a 2001 survey, it was found that only 28% of subjects reported receiving advice from their physicians to increase their physical activity [41]. Of the individuals who received advice, only 38% (or 11% total group) received help formulating a specific activity plan, and 42% received follow-up support. As noted, in 2013, the AHA/ACC published obesity guidelines that specifically detail how primary care physicians can incorporate assessment and treatment for overweight and obesity into daily practice [112]. The recommendation to consider obesity as a disease and provide an algorithm for assessment and treatment was made due to continued undertreatment noted during systematic reviews in 1998 and 2005 [69,112].

According to the CDC, adults should engage in at least 150 minutes of moderate-intensity aerobic activity (e.g., brisk walking) or 75 minutes/week of vigorous-intensity exercise (e.g., jogging, running) every week, combined with muscle-strengthening activities that work all major muscle groups (legs, hips, back, abdomen, chest, shoulders, and arms) two or more days per week for moderate health benefits [83]. (Note: A weekly workout can include a mix of exercise intensity equal to the given recommendations.) For increased health benefits, moderate-intensity aerobic exercise should be doubled to 300 minutes per week [83].

Pharmacotherapy should only be used as an adjunct to lifestyle modification, including calorie restriction and increased physical activity. It should not be used as a primary treatment option or by people who are unwilling to make behavioral changes. Rather, if lifestyle changes do not promote weight loss after six months, drugs should be considered. Most drugs are recommended for use in patients with a BMI >30 or in those with a BMI >27 and comorbidities such as type 2 diabetes, hypertension, or sleep apnea [128]. Many pharmacotherapies combined with exercise and lifestyle modification are effective in achieving meaningful weight reduction; the more elusive goal has been maintenance of healthy weight required to alleviate comorbidities (e.g., type 2 diabetes) and prevent potential complications (e.g., cardiovascular disease) of obesity.

As of 2014, four drugs (orlistat, phentermine/topiramate, liraglutide, and bupropion/naltrexone) were approved by the U.S. Food and Drug Administration (FDA) for long-term weight loss. Orlistat is available either by prescription (brand name Xenical) or over the counter (brand name Alli). Phentermine/topiramate (brand name Qsymia), liraglutide (brand name Saxenda), and bupropion/naltrexone (brand name Contrave) are available by prescription only. These weight-loss agents work by suppressing appetite or blocking pancreatic lipase.

Orlistat is contraindicated in patients with chronic malabsorption syndrome or cholestasis, and it should be used with caution in patients taking cyclosporine. Side effects of orlistat include, but are not limited to, steatorrhea, incontinence, and diarrhea. Dietary supplementation with fat-soluble vitamins is recommended. Cases of acute kidney injury from oxalate crystal deposition have been reported in 2% of patients within one year of initiating orlistat [128]. Renal function should be monitored in patients receiving orlistat, particularly those at increased risk because of age or pre-existing renal dysfunction. Rarely, patients taking orlistat have developed severe liver injury, and this risk should be weighed against potential benefits [71].

In 2012, the FDA approved phentermine/topiramate, one of the first new weight-loss mediations in more than a decade [98]. Phentermine/topiramate (extended-release) combines an anorexiant and an anticonvulsant to improve short-term weight-loss outcomes in patients who have already attempted lifestyle changes (i.e., calorie-restricted diet and increased physical activity) [95]. Eligible patients will have a BMI ≥30 or a BMI ≥27 with a weight-related comorbidity [98]. In two randomized, placebo-controlled trials involving approximately 3,700 obese and overweight patients, phentermine/topiramate was found to be effective and safe if used correctly [98]. After one year, patients taking phentermine/topiramate experienced 6.7% (at the recommended dose) to 8.9% (at the highest dose) greater weight loss compared to those taking placebo. More than 60% of participants taking phentermine/topiramate recorded at least a 5% decrease in their body weight, compared to only 20% of the placebo group [98].

The recommended initial dose of phentermine/topiramate is 7.5 mg phentermine/46 mg topiramate extended-release once per day [98]. If weight reduction is <3% at 12 weeks, the dose may be titrated to a maximum of 15 mg/92 mg. The medication is contraindicated in persons with glaucoma, uncontrolled hypertension, or hyperthyroidism, and is not recommended for patients with a recent history of stroke or heart disease [98,128]. It is also teratogenic, with proven fetal defects with first trimester exposure. Therefore, all women of childbearing age should use effective contraception consistently while taking the drug and have documented proof of a negative pregnancy test prior to the initiation of treatment and every month thereafter [98].

In 2014, combination bupropion/naltrexone was approved as a treatment option for chronic weight management [99]. Studies show that these drugs are effective in improving the percentage of total body weight lost compared to placebo [84,99]. The dosage is gradually titrated up, starting with one tablet (naltrexone 8 mg/bupropion 90 mg) once daily in the morning for one week and increasing one daily tablet each week for four weeks. The maintenance dose is two tablets twice daily [71]. If 5% of initial body weight has not been lost after 12 weeks, the medication should be discontinued.

Any patient taking bupropion should be carefully monitored for suicidal ideation and behaviors [99]. This medication may also increase blood pressure and heart rate and is contraindicated in patients with hypertension. It also should be avoided in patients with opioid dependence, a history of seizures, or who are pregnant.

When pharmacotherapy is effective, weight loss should exceed 2 kg (4.4 lbs) during the first month and weight should decrease by about 5% of baseline within six months. Pharmacotherapy should be discontinued if weight loss is not achieved. In cases in which the therapeutic goal includes significant metabolic improvement in addition to weight loss (e.g., a patient with type 2 diabetes), failure to achieve a 5% decline in weight at three months warrants consideration of alternative pharmacotherapy or bariatric surgery [129]. When it is successful, pharmacotherapy with orlistat may be continued past one year; data is currently available to four years with orlistat [71]. Patients should keep in mind that weight loss typically stabilizes after six months of treatment, and weight gain can occur when pharmacologic therapy is discontinued.

In 2014, researchers conducted a systematic review to compare available FDA-approved drugs for short- and long-term weight loss using existing meta-analyses, systematic reviews, and randomized, placebo-controlled trials [114]. Combined with prescribed lifestyle changes, weight loss was noted at one year at approximately 3% for both orlistat and lorcaserin, and 9% for maximum-dose phentermine/topiramate compared with placebo [114]. Clinically meaningful weight loss (defined as ≥5% of initial weight in one year) was 37% to 47% for lorcaserin, 35% to 73% for orlistat, and 67% to 70% for maximum-dose phentermine/topiramate [114]. There were no short-term weight loss drugs that met the inclusion criteria for the analysis. Additional research, with the inclusion of the two more recently FDA-approved drugs (bupropion/naltrexone and liraglutide) is required to provide more information on the drug that provides the greatest efficacy [114].

Several drugs are approved for short-term use in obese patients. These include sympathomimetic agents such as benzphetamine, methamphetamine, phentermine, phendimetrazine, and diethylpropion [71,114]. Data on long-term safety have not been demonstrated. Given that weight loss therapy is focused on long-term success, use of these drugs is rarely recommended. Leptin resistance may be a contributing factor to obesity in some cases, and leptin is being explored as a possible treatment.

The American Society for Metabolic and Bariatric Surgery (ASMBS) and the Society of American Gastrointestinal Endoscopic Surgeons have reaffirmed the 1991 National Institutes of Health guideline, which states that surgery is indicated for adult patients with a BMI greater than 40 or greater than 35 with significant comorbid conditions and who can demonstrate that dietary attempts at weight loss have failed [56,57]. In 2022, guidelines from the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) and ASMBS were released establishing the criteria for candidates for bariatric surgery as BMI ≥35, regardless of presence, absence, or severity of obesity-related complication, or BMI ≥30 in patients with type 2 diabetes [96]. Further, surgery should also be considered in patients with BMI 30–35 who do not achieve substantial or durable weight loss or obesity-related complication improvement nonsurgically. In 2019, the AACE/TOS/ASMBS/Obesity Medicine Association (OMA)/American Society of Anesthesiologists (AASA) guidelines further added a recommendation that the BMI requirement for bariatric surgery should be adjusted for ethnicity (e.g., 18.5 to 22.9 is normal range, 23 to 24.9 is overweight, and ≥25 is obesity for Asian patients) [97]. The 2022 ASMBS guideline recommends BMI thresholds be adjusted in Asian populations, and those with BMI >27.5 should be offered surgery ]96].

In 2016, 45 professional societies, including the American Diabetes Association, issued a joint statement that metabolic surgery should be considered for patients with type 2 diabetes and a BMI 30.0–34.9 if hyperglycemia is inadequately controlled despite optimal treatment with either oral or injectable medications [98].

Bariatric surgery for patients older than 60 years of age has typically not been recommended. Patients should be thoroughly screened for a willingness to make lifestyle changes, as well as for any psychologic disorders that would impair a successful postoperative course. Surgical treatment is not a cosmetic procedure. It does not involve the removal of adipose tissue by suction or excisions; rather, it involves reducing the size of the stomach, with or without a degree of malabsorption.

Bariatric surgery does have complications. Approximately 10% to 20% of all patients who have weight-loss surgery require follow-up operations. Gastric bypass operations may cause "dumping syndrome," whereby stomach contents move too rapidly through the small intestine. Typically, this is caused by the high osmolarity of simple carbohydrates in the intestine. The higher concentration causes fluids to shift towards the higher osmolarity. This results in additional fluid in the bowel, which causes it to be stretched, with subsequent pain and nausea. Activation of hormonal and nerve responses causes increased heart rate. There may be vomiting and diarrhea. A short time later, there typically is a glucose spike, as the small bowel absorbs sugar. The pancreas responds by secreting insulin, which then causes hypoglycemia, causing weakness and light-headedness. Dumping syndrome should be monitored carefully.

Abdominal hernias can also occur, requiring follow-up surgery. More than one-third of obese patients who have gastric surgery develop gallstones. Post-operative complications may include deep vein thrombosis, pulmonary emboli, bleeding, band migration, and infection. Possible later complications include breakdown of the staple line or band erosion, causing internal infections.

Depending on the type of procedure, nearly 30% of patients who have weight-loss surgery can develop nutritional deficiencies such as anemia, osteoporosis, and metabolic bone disease. Therefore, it is important that patients take supplemental vitamins and minerals.

Because bariatric surgical procedures are still evolving, true surgical mortality rates are uncertain. The overall risk of death from gastric bypass appears to be less than 0.2% at 30 days and varies by the type of procedure [105]. Older data, gathered between 1987 and 2001, suggested a 30-day mortality rate as high as 1.9%, but outcomes have improved as surgeons gained experience and lower-risk patients sought treatment [55]. The increase in laparoscopic procedures has contributed to a lower risk of death. It is estimated that the 30-day mortality rate is 0.14% for laparoscopic gastric bypass, 0.08% for laparoscopic sleeve gastrectomy, and 0.03% for laparoscopic gastric banding [105].

Intragastric balloon systems, brand names Orbera and the ReShape Integrated Balloon System, were approved by the FDA in 2015. These systems are intended as a minimally invasive, short-term treatment, involving placement in the stomach of an inflatable, free-floating balloon. They are intended to be used in conjunction with diet and exercise. Both Orbera and ReShape are placed into the stomach through the mouth with the patient under mild sedation, using a minimally invasive endoscopic procedure. These balloons are then filled with 400–700 cc of saline (ReShape also adds methylene blue dye) to restrict the amount of space in the stomach. These balloons may be placed for up to six months. A third balloon system, brand name Obalon, was approved by the FDA in 2016 and consists of up to three balloons in a capsule that is attached to a thin inflation catheter. The balloons are swallowed and then inflated with air to reduce amount of free space in the stomach [117].