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Obesity

By

Adrienne Youdim

, MD, David Geffen School of Medicine at UCLA

Last full review/revision Aug 2021| Content last modified Aug 2021
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Obesity is excess body weight, defined as a body mass index (BMI) of ≥ 30 kg/m2. Complications include cardiovascular disorders (particularly in people with excess abdominal fat), diabetes mellitus, certain cancers, cholelithiasis, fatty liver, cirrhosis, osteoarthritis, reproductive disorders in men and women, psychologic disorders, and, for people with BMI ≥ 35, premature death. Diagnosis is based on BMI. Treatment includes lifestyle modification (eg, in diet, physical activity, and behavior) and, for certain patients, drugs or bariatric (weight-loss) surgery.

Prevalence of obesity in the US is high in all age groups (see table Changes in Prevalence of Obesity According to NHANES Changes in Prevalence of Obesity According to NHANES Obesity is excess body weight, defined as a body mass index (BMI) of ≥ 30 kg/m2. Complications include cardiovascular disorders (particularly in people with excess abdominal fat), diabetes mellitus... read more ). In 2017-2018, 42.4% of adults were obese (1 General reference Obesity is excess body weight, defined as a body mass index (BMI) of ≥ 30 kg/m2. Complications include cardiovascular disorders (particularly in people with excess abdominal fat), diabetes mellitus... read more ). Prevalence was lowest among non-Hispanic Asian adults (17.4%) as compared to non-Hispanic black (49.6%), Hispanic (44.8%), and non-Hispanic white (42.2%) adults. There were no significant differences in prevalence between men and women among non-Hispanic white, non-Hispanic Asian, or Hispanic adults; however, prevalence among non-Hispanic black women (56.9%) was higher than all other groups.

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In the US, obesity and its complications cause as many as 300,000 premature deaths each year, making it second only to cigarette smoking as a preventable cause of death.

General reference

  • 1. Hales CM, Carroll MD, Fryar CD, et al: Prevalence of obesity and severe obesity among adults: United States, 2017–2018. NCHS Data Brief, no 360. Hyattsville, MD: National Center for Health Statistics, 2020.

Etiology of Obesity

Causes of obesity are probably multifactorial and include genetic predisposition. Ultimately, obesity results from a long-standing imbalance between energy intake and energy expenditure, including energy utilization for basic metabolic processes and energy expenditure from physical activity. However, many other factors appear to increase a person's predisposition to obesity, including endocrine disruptors (eg, bisphenol A [BPA]), gut microbiome, sleep/wake cycles, and environmental factors.

Genetic factors

Heritability of BMI is about 66%. Genetic factors may affect the many signaling molecules and receptors used by parts of the hypothalamus and gastrointestinal tract to regulate food intake (see sidebar Pathways Regulating Food Intake Pathways Regulating Food Intake Obesity is excess body weight, defined as a body mass index (BMI) of ≥ 30 kg/m2. Complications include cardiovascular disorders (particularly in people with excess abdominal fat), diabetes mellitus... read more ). Genetic factors can be inherited or result from conditions in utero (called genetic imprinting). Rarely, obesity results from abnormal levels of peptides that regulate food intake (eg, leptin) or abnormalities in their receptors (eg, melanocortin-4 receptor).

Pathways Regulating Food Intake

Preabsorptive and postabsorptive signals from the gastrointestinal tract and changes in plasma nutrient levels provide short- and long-term feedback to regulate food intake:

  • Gastrointestinal hormones (eg, glucagon-like peptide 1 [GLP-1], cholecystokinin [CCK], peptide YY [PYY]) reduce food intake.

  • Ghrelin, secreted primarily by the stomach, increases food intake.

  • Leptin, secreted from adipose tissue, informs the brain how much fat is stored. Leptin suppresses appetite in normal-weight people, but high leptin levels correlate with increased body fat. Leptin levels can decrease when weight is lost and then send a hunger signal to the brain.

The hypothalamus integrates various signals involved in the regulation of energy balance and then activates pathways that increase or decrease food intake:

  • Neuropeptide Y (NPY), agouti-related peptide (ARP), alpha-melanocyte–stimulating hormone (alpha-MSH), cocaine- and amphetamine-related transcript (CART), orexin, and melanin-concentrating hormone (MCH) increase food intake.

  • Corticotropic hormone (CRH) and urocortin decrease it.

The limbic system (amygdala, hippocampus, and prefrontal cortex) mediates the hedonistic pathway for food intake, including cravings, habit, and reward. The desire to eat can override homeostatic pathways because emotion and stress have been shown to affect regulatory peptides such as ghrelin. These effects are mediated by dopamine.

Genetic factors also regulate energy expenditure, including basal metabolic rate, diet-induced thermogenesis, and nonvoluntary activity–associated thermogenesis. Genetic factors may have a greater effect on the distribution of body fat, particularly abdominal fat (which increases the risk of metabolic syndrome Metabolic Syndrome Metabolic syndrome is characterized by a large waist circumference (due to excess abdominal fat), hypertension, abnormal fasting plasma glucose or insulin resistance, and dyslipidemia. Causes... read more ), than on the amount of body fat.

Environmental factors

Weight is gained when caloric intake exceeds energy needs. Important determinants of energy intake include

  • Portion sizes

  • The energy density of the food

High-calorie foods (eg, processed foods), diets high in refined carbohydrates, and consumption of soft drinks, fruit juices, and alcohol promote weight gain. Diets high in fresh fruit and vegetables, fiber, complex carbohydrates, and lean proteins, with water as the main fluid consumed, minimize weight gain.

A sedentary lifestyle promotes weight gain.

Regulatory factors

Prenatal maternal obesity, prenatal maternal smoking, and intrauterine growth restriction can disturb weight regulation and contribute to weight gain during childhood and later. Obesity that persists beyond early childhood makes weight loss in later life more difficult.

The composition of the gut microbiome also appears to be an important factor; early use of antibiotics and other factors that alter the composition of the gut microbiome may promote weight gain and obesity later in life (1 Etiology references Obesity is excess body weight, defined as a body mass index (BMI) of ≥ 30 kg/m2. Complications include cardiovascular disorders (particularly in people with excess abdominal fat), diabetes mellitus... read more ).

Early exposure to obesogens, a type of endocrine-disrupting chemical (eg, cigarette smoke, bisphenol A, air pollution, flame retardants, phthalates, polychlorinated biphenyls) can alter metabolic set points through epigenetics or nuclear activation, increasing the propensity of developing obesity (2 Obesity is excess body weight, defined as a body mass index (BMI) of ≥ 30 kg/m2. Complications include cardiovascular disorders (particularly in people with excess abdominal fat), diabetes mellitus... read more ).

Adverse childhood events or abuse in early childhood increase risk of several disorders, including obesity. The Centers for Disease Control and Prevention's adverse childhood events study demonstrated that childhood history of verbal, physical, or sexual abuse predicted an 8% increase risk of BMI ≥ 30 and 17.3% of BMI ≥ to 40. Certain types of abuse carried the strongest risk. For example, frequent verbal abuse had the largest increase in risk (88%) for BMI > 40. Being often hit and injured increased the risk of BMI > 30 by 71% (3 Etiology references Obesity is excess body weight, defined as a body mass index (BMI) of ≥ 30 kg/m2. Complications include cardiovascular disorders (particularly in people with excess abdominal fat), diabetes mellitus... read more ). Cited mechanisms for the association between abuse and obesity include neurobiologic and epigenetic phenomena (4 Etiology references Obesity is excess body weight, defined as a body mass index (BMI) of ≥ 30 kg/m2. Complications include cardiovascular disorders (particularly in people with excess abdominal fat), diabetes mellitus... read more ).

About 15% of women permanently gain ≥ 20 lb with each pregnancy.

Insufficient sleep (usually considered < 6 to 8 hours/night) can result in weight gain by changing the levels of satiety hormones that promote hunger.

Drugs, including corticosteroids, lithium, traditional antidepressants (tricyclics, tetracyclics, monoamine oxidase inhibitors [MAOIs]), benzodiazepines, antiseizure drugs, thiazolidinediones (eg, rosiglitazone, pioglitazone), beta-blockers, and antipsychotic drugs, can cause weight gain.

Uncommonly, weight gain is caused by one of the following disorders:

Eating disorders

At least 2 pathologic eating patterns may be associated with obesity:

Similar but less extreme patterns probably contribute to excess weight gain in more people. For example, eating after the evening meal contributes to excess weight gain in many people who do not have night-eating syndrome.

Etiology references

  • 1. Ajslev TA, Andersen CS, Gamborg M, et al: Childhood overweight after establishment of the gut microbiota: The role of delivery mode, pre-pregnancy weight and early administration of antibiotics. Int J Obes 35 (4): 522–529, 2011. doi: 10.1038/ijo.2011.27

  • 2. Heindel JJ, Newbold R, Schug TT: Endocrine disruptors and obesity. Nat Rev Endocrinol 11 (11):653–661, 2015. doi: 10.1038/nrendo.2015.163

  • 3. Williamson DF, Thompson TJ, Anda RF, et al: Body weight and obesity in adults and self-reported abuse in childhood. Int J Obes Relat Metab Disord 26(8):1075-82, 2002. doi: 10.1038/sj.ijo.0802038

  • 4. Anda RF, Felitti VJ, Bremner JD, et al: The enduring effects of abuse and related adverse experiences in childhood. A convergence of evidence from neurobiology and epidemiology. Eur Arch Psychiatry Clin Neurosci 256(3):174-86, 2006. doi: 10.1007/s00406-005-0624-4

Complications of Obesity

Complications of obesity include the following:

Insulin resistance Type 2 diabetes Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more , dyslipidemias Dyslipidemia Dyslipidemia is elevation of plasma cholesterol, triglycerides (TGs), or both, or a low high-density lipoprotein cholesterol level that contributes to the development of atherosclerosis. Causes... read more Dyslipidemia , and hypertension Hypertension Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more Hypertension (metabolic syndrome) can develop, often leading to diabetes mellitus Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more and coronary artery disease Overview of Coronary Artery Disease Coronary artery disease (CAD) involves impairment of blood flow through the coronary arteries, most commonly by atheromas. Clinical presentations include silent ischemia, angina pectoris, acute... read more Overview of Coronary Artery Disease . These complications are more likely in patients with fat that is concentrated abdominally (visceral fat), a high serum triglyceride level, a family history of type 2 diabetes mellitus or premature cardiovascular disease, or a combination of these risk factors.

Obesity may cause the obesity-hypoventilation syndrome (Pickwickian syndrome). Impaired breathing leads to hypercapnia, reduced sensitivity to carbon dioxide in stimulating respiration, hypoxia, cor pulmonale, and risk of premature death. This syndrome may occur alone or secondary to obstructive sleep apnea.

Skin disorders are common; increased sweat and skin secretions, trapped in thick folds of skin, are conducive to fungal and bacterial growth, making intertriginous infections especially common.

Obesity leads to social, economic, and psychologic problems as a result of prejudice, discrimination, poor body image, and low self-esteem. For example, people may be underemployed or unemployed.

Diagnosis of Obesity

  • Body mass index (BMI)

  • Waist circumference

  • Sometimes body composition analysis

  • Overweight = 25 to 29.9 kg/m2

  • Obesity = 30 kg/m2

However, BMI is a crude screening tool and has limitations in many subpopulations. Some experts think that BMI cutoffs should vary based on ethnicity, sex, and age. For example, in certain nonwhite populations, complications of obesity develop at a much lower BMI than in whites.

In children and adolescents, overweight is defined as BMI at the 95th percentile, based on the Centers for Disease Control and Prevention's age- and sex-specific growth charts.

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Asians and many aboriginal populations have a lower cut-off (23 kg/m2) for overweight. In addition, BMI may be high in muscular athletes, who lack excess body fat, and may be normal or low in formerly overweight people who have lost muscle mass.

Waist circumference and the presence of metabolic syndrome appear to predict risk of metabolic and cardiovascular complications better than BMI does.

The waist circumference that increases risk of complications due to obesity varies by ethnic group and sex.

Body composition analysis

Body composition—the percentage of body fat and muscle—is also considered when obesity is diagnosed. Although probably unnecessary in routine clinical practice, body composition analysis can be helpful if clinicians question whether elevated BMI is due to muscle or excessive fat.

Bioelectrical impedance analysis (BIA) can estimate percentage of body fat simply and noninvasively. BIA estimates percentage of total body water directly; percentage of body fat is derived indirectly. BIA is most reliable in healthy people and in people with only a few chronic disorders that do not change the percentage of total body water (eg, moderate obesity, diabetes mellitus). Whether measuring BIA poses risks in people with implanted defibrillators is unclear.

Underwater (hydrostatic) weighing is the most accurate method for measuring percentage of body fat. Costly and time-consuming, it is used more often in research than in clinical care. To be weighed accurately while submerged, people must fully exhale beforehand.

Imaging procedures, including CT, MRI, and dual-energy x-ray absorptiometry (DXA), can also estimate the percentage and distribution of body fat but are usually used only for research.

Other testing

Obese patients should be screened for common comorbid disorders, such as obstructive sleep apnea Obstructive Sleep Apnea Obstructive sleep apnea (OSA) consists of episodes of partial or complete closure of the upper airway that occur during sleep and lead to breathing cessation (defined as a period of apnea or... read more , diabetes Screening for disease Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more , dyslipidemia Dyslipidemia Dyslipidemia is elevation of plasma cholesterol, triglycerides (TGs), or both, or a low high-density lipoprotein cholesterol level that contributes to the development of atherosclerosis. Causes... read more Dyslipidemia , hypertension Hypertension Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more Hypertension , fatty liver Nonalcoholic Fatty Liver Disease (NAFLD) Fatty liver is excessive accumulation of lipid in hepatocytes. Nonalcoholic fatty liver disease (NAFLD) includes simple fatty infiltration (a benign condition called fatty liver), whereas nonalcoholic... read more , and depression Diagnosis Depressive disorders are characterized by sadness severe enough or persistent enough to interfere with function and often by decreased interest or pleasure in activities. Exact cause is unknown... read more . Screening tools can help; for example, for obstructive sleep apnea, clinicians can use an instrument such as the STOP-BANG questionnaire (see table STOP-BANG Risk Score for Obstructive Sleep Apnea STOP-BANG Risk Score for Obstructive Sleep Apnea Almost half of all people in the US report sleep-related problems. Disordered sleep can cause emotional disturbance, memory difficulty, poor motor skills, decreased work efficiency, and increased... read more ) and often the apnea-hypopnea index Obstructive sleep apnea (OSA) consists of episodes of partial or complete closure of the upper airway that occur during sleep and lead to breathing cessation (defined as a period of apnea or... read more (total number of apnea or hypopnea episodes occurring per hour of sleep). Obstructive sleep apnea is often underdiagnosed, and obesity increases the risk.

Prognosis of Obesity

Untreated, obesity tends to progress. The probability and severity of complications are proportional to

  • The absolute amount of fat

  • The distribution of the fat

  • Absolute muscle mass

After weight loss, most people return to their pretreatment weight within 5 years, and accordingly, obesity requires a lifelong management program similar to that for any other chronic disorder.

Treatment of Obesity

  • Dietary management

  • Physical activity

  • Behavioral interventions

  • Drugs (eg, phentermine, orlistat, lorcaserin [not available in US because of possible cancer risk], phentermine/topiramate, naltrexone/bupropion extended-release, liraglutide, semaglutide)

  • Bariatric surgery

Weight loss of even 5 to 10% improves overall health, helps reduce risk of developing cardiovascular complications (eg, hypertension Hypertension Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more Hypertension , dyslipidemia Dyslipidemia Dyslipidemia is elevation of plasma cholesterol, triglycerides (TGs), or both, or a low high-density lipoprotein cholesterol level that contributes to the development of atherosclerosis. Causes... read more Dyslipidemia , insulin resistance Type 2 diabetes Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more ) and helps lessen their severity, and may lessen the severity of other complications and comorbid disorders such as obstructive sleep apnea Obstructive Sleep Apnea Obstructive sleep apnea (OSA) consists of episodes of partial or complete closure of the upper airway that occur during sleep and lead to breathing cessation (defined as a period of apnea or... read more , fatty liver Nonalcoholic Fatty Liver Disease (NAFLD) Fatty liver is excessive accumulation of lipid in hepatocytes. Nonalcoholic fatty liver disease (NAFLD) includes simple fatty infiltration (a benign condition called fatty liver), whereas nonalcoholic... read more , infertility Overview of Infertility Infertility is usually defined as inability of a couple to conceive after 1 year of unprotected intercourse. Infertility is defined as a disease by the World Health Organization (WHO). Frequent... read more , and depression Depressive Disorders Depressive disorders are characterized by sadness severe enough or persistent enough to interfere with function and often by decreased interest or pleasure in activities. Exact cause is unknown... read more .

Support from health care practitioners, peers, and family members and various structured programs can help with weight loss and weight maintenance.

Diet

Balanced eating is important for weight loss and maintenance.

Strategies include

  • Eating small meals and avoiding or carefully choosing snacks

  • Substituting fresh fruits and vegetables and salads for refined carbohydrates and processed food

  • Substituting water for soft drinks or juices

  • Limiting alcohol consumption to moderate levels

  • Including no- or low-fat dairy products, which are part of a healthy diet and help provide an adequate amount of vitamin D

Use of meal replacements can help with weight loss and maintenance; these products can be used regularly or intermittently.

Diets that are overly restrictive are unlikely to be maintained or to result in long-term weight loss. Diets that limit caloric intake to < 50% of basal energy expenditure Energy expenditure Many undernourished patients need nutritional support, which aims to increase lean body mass. Oral feeding can be difficult for some patients with anorexia or with eating or absorption problems... read more (BEE), described as very low calorie diets, can have as few as 800 kcal/day. A very low calorie diet may be indicated for obese patients; however, such diets must be supervised by a physician, and after weight is lost, intake must be increased gradually to prevent patients from regaining weight.

Physical activity

Exercise increases energy expenditure, basal metabolic rate, and diet-induced thermogenesis. Exercise also seems to regulate appetite to more closely match caloric needs. Other benefits associated with physical activity include

  • Increased insulin sensitivity

  • Improved lipid profile

  • Lower blood pressure

  • Better aerobic fitness

  • Improved psychologic well-being

  • Decreased risk of breast and colon cancer

  • Increased life expectancy

Exercise, including strengthening (resistance) exercises, increases muscle mass. Because muscle tissue burns more calories at rest than does fat tissue, increasing muscle mass produces lasting increases in basal metabolic rate. Exercise that is interesting and enjoyable is more likely to be sustained. A combination of aerobic and resistance exercise is better than either alone. Guidelines suggest physical activity of 150 minutes/week for health benefits and 300 to 360 minutes/week for weight loss and maintenance. Developing a more physically active lifestyle can help with weight loss and maintenance.

Behavioral interventions

Clinicians can recommend various behavioral interventions to help patients lose weight. They include

  • Support

  • Self-monitoring

  • Stress management

  • Contingency management

  • Problem solving

  • Stimulus control

Support may come from a group, a buddy, or family members. Participation in a support group can improve adherence to lifestyle changes and thus increase weight loss. The more frequently people attend group meetings, the greater the support, motivation, and supervision they receive and the greater their accountability, resulting in greater weight loss.

Self-monitoring may include keeping a food log (including the number of calories in foods), weighing regularly, and observing and recording behavioral patterns. Other useful information to record includes time and location of food consumption, the presence or absence of other people, and mood. Clinicians can provide feedback about how patients may improve their eating habits.

Stress management involves teaching patients to identify stressful situations and to develop strategies to manage stress that do not involve eating (eg, going for a walk, meditating, deep breathing).

Contingency management involves providing tangible rewards for positive behaviors (eg, for increasing time spent walking or reducing consumption of certain foods). Rewards may be given by other people (eg, from members of a support group or a health care practitioner) or by the person (eg, purchase of new clothing or tickets to a concert). Verbal rewards (praise) may also be useful.

Problem solving involves identifying and planning ahead for situations that increase the risk of unhealthy eating (eg, travelling, going out to dinner) or that reduce the opportunity for physical activity (eg, driving across country).

Stimulus control involves identifying obstacles to healthy eating and an active lifestyle and developing strategies to overcome them. For example, people may avoid going by a fast food restaurant or not keep sweets in the house. For a more active lifestyle, they may take up an active hobby (eg, gardening), enroll in scheduled group activities (eg, exercise classes, sports teams), walk more, make a habit of taking the stairs instead of elevators, and park at the far end of parking lots (resulting in a longer walk).

Internet resources, applications for mobile devices, and other technological devices may also help with adherence to lifestyle changes and weight loss. Applications can help patients set a weight-loss goal, monitor their progress, track food consumption, and record physical activity.

Drugs

Orlistat inhibits intestinal lipase, decreasing fat absorption and improving blood glucose and lipids. Because orlistat is not absorbed, systemic effects are rare. Flatus, oily stools, and diarrhea are common but tend to resolve during the 2nd year of treatment. A dose of 120 mg orally 3 times a day should be taken with meals that include fat. A vitamin supplement should be taken at least 2 hours before or after taking orlistat. Malabsorption and cholestasis are contraindications; irritable bowel syndrome and other gastrointestinal disorders may make orlistat difficult to tolerate. Orlistat is available over-the-counter.

Phentermine is a centrally acting appetite suppressant for short-term use ( ≤ 3 months). Usual starting dose is 15 mg once/day, and dose may be increased to 30 mg once/day, 37.5 mg once/day, 15 mg twice a day, or 8 mg 3 times a day before meals. Common side effects include elevated blood pressure and heart rate, insomnia, anxiety, and constipation. Phentermine should not be used in patients with preexisting cardiovascular disorders, poorly controlled hypertension, hyperthyroidism, or a history of drug abuse or addiction. Twice a day dosing may help control appetite better throughout the day.

The combination of phentermine and topiramate (used to treat seizures and migraines) is approved for long-term use. This combination drug results in weight loss for up to 2 years. The starting dose of the extended-release form (phentermine 3.75 mg/topiramate 23 mg) should be increased to 7.5 mg/46 mg after 2 weeks; then the dose can be gradually increased to a maximum of 15 mg/92 mg if needed to maintain weight loss. Because birth defects are a risk, the combination should be given to women of reproductive age only if they are using contraception and are tested monthly for pregnancy. Other potential adverse effects include sleep problems, cognitive impairment, and increased heart rate. Long-term cardiovascular effects are unknown, and postmarketing studies are ongoing.

Lorcaserin (not available in the US) suppresses appetite via selective agonism of serotonin 2C (5-HT2C) brain receptors. Unlike serotonergic drugs previously used for weight loss, lorcaserin selectively targets 5-HT2C receptors in the hypothalamus, which, when targeted, result in hypophagia; it does not to stimulate the 5-HT2B receptors on heart valves. In clinical studies, incidence of valvulopathy was not significantly increased in patients taking lorcaserin compared with those taking placebo. The usual and maximum dose of lorcaserin is 10 mg orally every 12 hours. The most common adverse effects in patients without diabetes are headache, nausea, dizziness, fatigue, dry mouth, and constipation; these effects are usually self-limited. Lorcaserin should not be used with serotonergic drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), or monoamine oxidase inhibitors (MAOIs), because serotonin syndrome Serotonin Syndrome Serotonin syndrome is a potentially life-threatening condition resulting from increased central nervous system serotonergic activity that is usually drug related. Symptoms may include mental... read more is a risk. Lorcaserin was withdrawn from the US market after an increased cancer risk was identified in a postmarketing trial.

Naltrexone/bupropion extended-release tablets can be used as a weight-loss adjunct. Naltrexone (used to aid in alcohol cessation) is an opioid antagonist and is thought to block negative feedback on satiety pathways in the brain. Bupropion (used to treat depression and aid in smoking cessation) can induce hypophagia by adrenergic and dopaminergic activity in the hypothalamus. The starting dose is a single tablet of naltrexone 8 mg/bupropion 90 mg; dose is titrated over 4 weeks to the maximum dose of 2 tablets twice a day. The most common adverse effects include nausea, vomiting, headache, and increases in systolic and diastolic blood pressure of 1 to 3 mm Hg. Contraindications to this drug include uncontrolled hypertension and a history of or risk factors for seizures because bupropion reduces the seizure threshold.

Liraglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist used initially in the treatment of type 2 diabetes. Liraglutide augments glucose-mediated insulin release from the pancreas to induce glycemic control; liraglutide also stimulates satiety and reduces food intake. Studies have shown that liraglutide 3 mg daily results in a 12.2% weight loss after 56 weeks. The initial dose is 0.6 mg injected subcutaneously once/day; the dose is increased 0.6 mg/week to the maximum dose of 3 mg once/day. Liraglutide must be given by injection. Adverse effects include nausea and vomiting; liraglutide has warnings that include acute pancreatitis and risk of thyroid C-cell tumors.

Semaglutide is a GLP-1 receptor agonist approved for the treatment of type 2 diabetes. Semaglutide augments glucose-mediated insulin release and reduces appetite and energy intake via effects on appetite centers in the hypothalamus. Semaglutide 2.4 mg subcutaneously has resulted in a mean body weight loss of 14.9% at 68 weeks as compared to 2.4% in patients treated with placebo (1 Treatment reference Obesity is excess body weight, defined as a body mass index (BMI) of ≥ 30 kg/m2. Complications include cardiovascular disorders (particularly in people with excess abdominal fat), diabetes mellitus... read more ). Patients on semaglutide also had greater improvements in cardiovascular risk factors as well as patient-reported physical functioning. Like liraglutide, the most common adverse effects of semaglutide include nausea and diarrhea, which are usually transient and mild to moderate in severity. Warnings for semaglutide include thyroid tumors and pancreatitis. The starting dose is 0.25 mg once a week for 4 weeks, increasing every 4 weeks to the maintenance dose of 2.4 mg once a week by week 17.

Weight-loss drugs should be stopped if patients do not have documented weight loss after 12 weeks of treatment.

Most over-the-counter weight-loss drugs are not recommended because they have not been shown to be effective. Examples of such drugs are brindleberry, L-carnitine, chitosan, pectin, grapeseed extract, horse chestnut, chromium picolinate, fucus vesiculosus, and ginkgo biloba. Some (eg, caffeine, ephedrine, guarana, phenylpropanolamine) have adverse effects that outweigh their advantages. Also, some of these drugs are adulterated or contain harmful substances banned by the US Food and Drug Administration (eg, ephedra, bitter orange, sibutramine).

Surgery

Treatment reference

Special Populations

Obesity is a particular concern in children and older adults.

Children

For obese children, complications are more likely to develop because they are obese longer. More than 25% of children and adolescents are overweight or obese. (See also Obesity in Adolescents Obesity in Adolescents Obesity is now twice as common among adolescents than it was 30 years ago and is one of the most common reasons for visits to adolescent clinics. Although fewer than one third of obese adults... read more .)

After puberty, food intake increases; in boys, the extra calories are used to increase protein deposition, but in girls, fat storage is increased.

For obese children, psychologic complications (eg, poor self-esteem, social difficulties, depression) and musculoskeletal complications can develop early. Some musculoskeletal complications, such as slipped capital femoral epiphyses Slipped Capital Femoral Epiphysis (SCFE) Slipped capital femoral epiphysis is movement of the femoral neck upward and forward on the femoral epiphysis. Diagnosis is with x-rays of both hips; sometimes other imaging is needed. Treatment... read more Slipped Capital Femoral Epiphysis (SCFE) , occur only in children. Other early complications may include obstructive sleep apnea Obstructive Sleep Apnea in Children Obstructive sleep apnea (OSA) is episodes of partial or complete closure of the upper airway that occur during sleep and lead to breathing cessation. Symptoms include snoring and sometimes restless... read more , insulin resistance Type 2 diabetes Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more , hyperlipidemia, and nonalcoholic steatohepatitis Nonalcoholic Fatty Liver Disease (NAFLD) Fatty liver is excessive accumulation of lipid in hepatocytes. Nonalcoholic fatty liver disease (NAFLD) includes simple fatty infiltration (a benign condition called fatty liver), whereas nonalcoholic... read more . Risk of cardiovascular, respiratory, metabolic, hepatic, and other obesity-related complications increases when these children become adults.

Risk of obesity persisting into adulthood depends partly on when obesity first develops:

  • During infancy: Low risk

  • Between 6 months and 5 years: 25%

  • After 6 years: > 50%

  • During adolescence if a parent is obese: > 80%

In children, preventing further weight gain, rather than losing weight, is a reasonable goal. Diet should be modified, and physical activity increased. Increasing general activities and play is more likely to be effective than a structured exercise program. Participating in physical activities during childhood may promote a lifelong physically active lifestyle. Limiting sedentary activities (eg, watching TV, using the computer or handheld devices) can also help. Drugs and surgery are avoided but, if complications of obesity are life threatening, may be warranted.

Measures that control weight and prevent obesity in children may have the largest public health benefits. Such measures should be implemented in the family, schools, and primary care programs.

Older adults

In the US, the percentage of obese older people has been increasing.

With age, body fat increases and is redistributed to the abdomen, and muscle mass is lost, largely because of physical inactivity, but decreased androgens and growth hormone (which are anabolic) and inflammatory cytokines produced in obesity may also play a role.

Risk of complications depends on

  • Body fat distribution (increasing with a predominantly abdominal distribution)

  • Duration and severity of obesity

  • Associated sarcopenia

For older adults, physicians may recommend that caloric intake be reduced and physical activity be increased. However, if older patients wish to substantially reduce their caloric intake, their diet should be supervised by a physician. Physical activity also improves muscle strength, endurance, and overall well-being and reduces the risk of developing chronic disorders such as diabetes. Activity should include strengthening and endurance exercises.

Regardless of whether caloric restriction is considered necessary, nutrition should be optimized.

Prevention of Obesity

Regular physical activity and healthy eating improve general fitness, can control weight, and help prevent diabetes mellitus Type 2 diabetes Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more and obesity. Even without weight loss, exercise decreases the risk of cardiovascular disorders. Dietary fiber decreases the risk of colon cancer and cardiovascular disorders.

Sufficient and good-quality sleep, management of stress, and moderation of alcohol intake are also important.

Key Points

  • Obesity increases the risk of many common health problems and causes up to 300,000 premature deaths each year in the US, making it second only to cigarette smoking as a preventable cause of death.

  • Excess caloric intake and too little physical activity contribute the most to obesity, but genetic susceptibility and various disorders (including eating disorders) may also contribute.

  • Screen patients using BMI and waist circumference and, when body composition analysis is indicated, by measuring skinfold thickness or using bioelectrical impedance analysis.

  • Screen obese patients for common comorbid disorders, such as obstructive sleep apnea, diabetes, dyslipidemia, hypertension, fatty liver, and depression.

  • Encourage patients to lose even 5 to 10% of body weight by changing their diet, increasing physical activity, and using behavioral interventions if possible.

  • Try treating patients with orlistat, phentermine, phentermine/topiramate, naltrexone/bupropion, liraglutide, or semaglutide if BMI is ≥ 30 or if BMI is ≥ 27 and they have complications (eg, hypertension, insulin resistance); however, for severe obesity, surgery is most effective.

  • Encourage all patients to exercise, to eat healthily, to get enough sleep, and to manage stress.

Drugs Mentioned In This Article

Drug Name Select Trade
LEVOPHED
AVANDIA
ACTOS
VICTOZA
ADIPEX-P
Semaglutide
TOPAMAX
BELVIQ
REVIA
WELLBUTRIN, ZYBAN
AMBIEN
No US brand name
ALLI, XENICAL
LITHOBID
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Obesity and the Metabolic Syndrome
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Iodine
Which of the following minerals is involved primarily in the synthesis of thyroxine (T4)? 
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