Obesity Treatment & Management

Treatment of obesity starts with comprehensive lifestyle management (ie, diet, physical activity, behavior modification), which should include the following ^[11] :

• Self-monitoring of caloric intake and physical activity

• Goal setting

• Stimulus control

• Nonfood rewards

• Relapse prevention

As with all chronic medical conditions, effective management of obesity must be based on a partnership between a highly motivated patient and a committed team of health professionals. This team may include the physician, a psychologist or psychiatrist, physical and exercise therapists, dietitians, and other subspecialists, depending on the comorbidities of the individual patient. Scientific evidence indicates that multidisciplinary programs reliably produce and sustain modest weight loss between 5% and 10% for the long-term. ^{[114, 115]}

In January, 2015, the Endocrine Society released new guidelines on the treatment of obesity to include the following: ^{[116, 117]}

• Diet, exercise, and behavioral modification should be included in all obesity management approaches for body mass index (BMI) of 25 kg/m² or higher. Other tools, such as pharmacotherapy for BMI of 27 kg/m² or higher with comorbidity or BMI over 30 kg/m2 and bariatric surgery for BMI of 35 kg/m² with comorbidity or BMI over 40 kg/m², should be used as adjuncts to behavioral modification to reduce food intake and increase physical activity when this is possible.

• Drugs may amplify adherence to behavior change and may improve physical functioning such that increased physical activity is easier in those who cannot exercise initially. Patients who have a history of being unable to successfully lose and maintain weight and who meet label indications are candidates for weight loss medications.

• To promote long-term weight maintenance, the use of approved weight loss medication (over no pharmacological therapy) is suggested to ameliorate comorbidities and amplify adherence to behavior changes, which may improve physical functioning and allow for greater physical activity in individuals with a BMI of 30 kg/m² or higher or in individuals with a BME of 27 kg/m² and at least one associated comorbid medical condition (eg, hypertension, dyslipidemia, type 2 diabetes mellitus, and obstructive sleep apnea).

• If a patient's response to a weight loss medication is deemed effective (weight loss of 5% or more of body weight at 3 mo) and safe, it is recommended that the medication be continued. If deemed ineffective (weight loss less than 5% at 3 mo) or if there are safety or tolerability issues at any time, it is recommended that the medication be discontinued and alternative medications or referral for alternative treatment approaches be considered.

• In patients with type 2 diabetes mellitus who are overweight or obese, antidiabetic medications that have additional actions to promote weight loss (such as glucagonlike peptide-1 [GLP-1] analogs or sodium-glucose-linked transporter-2 [SGLT-2] inhibitors) are suggested, in addition to the first-line agent for type 2 diabetes mellitus and obesity, metformin.

• In obese patients with type 2 diabetes mellitus who require insulin therapy, at least one of the following is suggested: metformin, pramlintide, or GLP-1 agonists to mitigate associated weight gain due to insulin. The first-line insulin for this type of patient should be basal insulin. This is preferable to using either insulin alone or insulin with sulfonylurea.

• Angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and calcium channel blockers, rather than beta-adrenergic blockers, should be considered as first-line therapy for hypertension in patients with type 2 diabetes mellitus who are obese.

• In women with a BMI of 27 kg/m² or more with comorbidities or a BMI of 30 kg/m² or more, seeking contraception, oral contraceptives are suggested over injectable medications because of weight gain with injectables, provided that women are well informed about the risks and benefits (ie, oral contraceptives are not contraindicated).

Weight-loss programs

The 3 major phases of any successful weight-loss program are as follows:

• Preinclusion screening phase

• Weight-loss phase

• Maintenance phase - This can conceivably last for the rest of the patient's life but ideally lasts for at least 1 year after the weight-loss program has been completed

Evidence supports the use of commercial weight-loss programs. A 12-week randomized, controlled trial found that commercially available weight-loss programs are more successful and more affordable than primary care practice–based programs led by specially trained staff. ^[118]

Pharmacologic therapy

Few drugs are available for the treatment of obesity, and their effectiveness is limited to palliation (ie, production and maintenance of weight loss) rather than cure, with benefits fading when the drugs are stopped. Because all medications inherently have more risks than diet and exercise do, pharmacologic therapy should be used only in patients in whom the benefit justifies the risk. ^[119]

Surgery

In patients with morbid obesity associated with comorbidities, bariatric surgery is the only available therapeutic modality associated with clinically significant and relatively sustained weight loss. Well-performed bariatric surgery, in carefully selected patients and with a good multidisciplinary support team, substantially ameliorates the morbidities associated with severe obesity.

Comorbidities

The management of obesity is not complete without attention being paid to potential comorbidities. Addressing these issues can have profound effects on the patient's well-being and risk of morbidity and mortality.

According to guidelines released by the American College of Cardiology (ACC), the American Heart Association (AHA), and The Obesity Society (TOS) in 2013, weight loss should be encouraged at a BMI of 25 with just 1 comorbidity (instead of 2 as was the case in previous guidelines), and elevated waist circumference can be one of those comorbidities. ^{[114, 115]}

Weight-loss ̶ associated morbidity

Although obesity in itself is associated with increased morbidity and mortality, massive, poorly monitored weight loss and/or weight cycling can have equally dire consequences. Among the important potential complications to watch out for in the setting of weight loss are the following:

• Cardiac arrhythmias

• Electrolyte derangements - Hypokalemia is the most important of these

• Hyperuricemia

• Psychological sequelae - Including depression and the development of eating disorders (particularly binge-eating disorders)

• Cholelithiasis

Before enrolling any patient in a weight-loss program, the clinician must have a clear idea of that individual’s expectations. A patient with unrealistic expectations should not be enrolled until these are changed to realistic and attainable goals. The clinician should guide the patient who seeks weight reduction to create goals that fit the mnemonic SMART: Specific, Measurable, Attainable, Realistic, and Timely.

A specific goal has a much greater chance of being accomplished than a general goal does. To set a specific goal, the patient must answer the following 6 W questions:

• Who - Who is involved?

• What - What do I want to accomplish?

• Where - Identify a location

• When - Establish a time frame

• Which - Identify requirements and constraints

• Why - Identify specific reasons for or purpose or benefits of the goal

Also crucial is a clear assessment of the patient's level of motivation regarding the changes in diet, exercise, and behavior required to maintain weight loss. This assessment should be completed before the patient is enrolled in a weight-loss program.

Comprehensive, written, informed consent must be obtained and should address details of the expected weight loss and the required changes. Clinical judgment may support a less stringent approach in some situations.

Psychiatric comorbidities

Because of the potential harm of attempting weight loss in an unsuitable candidate, all patients to be enrolled in any surgical, medical, or other weight-loss program should be screened for serious mental illness (eg, severe or untreated depression) and for eating disorders.

Many of the psychological and psychiatric problems commonly associated with obesity are not contraindications to enrollment in a weight-loss program; for example, mild to moderate depression typically improves with weight loss. Nevertheless, clinicians and patients must be aware of these problems before enrollment. In addition, the clinician must ensure that any such problems are relatively stable, quiescent, or well managed before the patient begins a weight-loss program.

In general, body weight and body fat are tenaciously regulated. This underlies the challenge of weight loss and highlights the importance of setting realistic weight-loss goals. Recognition of this challenge, and of the value of modest weight loss, have led to a paradigm shift in the medical management of obesity from a goal of massive weight loss to one of maintaining the highest weight possible while still eliminating obesity-related comorbidities or reducing them to a minimum.

Available data suggest that a loss of approximately 10% of body weight in persons who are obese (body mass index [BMI] < 40 kg/m²) is associated with substantial health benefits regarding obesity-related comorbidities. ^[120] However, according to guidelines released by the American College of Cardiology (ACC), the American Heart Association (AHA), and The Obesity Society (TOS) in 2013, clinically meaningful health improvements can even be seen with weight loss in the range of 2%-5%. ^{[114, 115]}

A reasonable goal for weight loss in the setting of a medical treatment program is approximately 1-2 lb/wk. However, it is becoming increasingly apparent that the weight-loss goal for each patient must be individualized and cannot be unilaterally based on standard weight-for-height norms.

In addition to the patient’s weight, factors to consider when setting individualized weight loss goals are the weight of other family members, as well as the patient's cultural, ethnic, and racial background. A study of approximately 200 obese black women, the Obesity Reduction Black Intervention Trial (ORBIT), found evidence that greater weight loss can be achieved with a culturally adapted weight-loss program than with a more general health program. ^[121]

In ORBIT, the women randomized to a 6-month, culturally adapted program aimed at altering dietary and physical activity patterns (followed by 1 year of maintenance intervention) lost significantly more weight than did participants in a general program. Despite this success, however, the average weight loss in the culturally adapted program was still relatively modest, and the amount of weight loss varied greatly among the women in the program.

Evidence from the National Weight Control Registry (NWCR), which tracks indices and predictors in individuals who have lost at least 30 pounds and have maintained that loss for at least 1 year, suggests that patterns associated with successful weight maintenance include the following:

• Self-monitoring of weight

• Consumption of a low-fat diet

• Daily physical activity of approximately 60 minutes

• Minimal sedentary “screen time”

• Consumption of most meals at home

Although some data from randomized trials of diets of different macronutrient composition indicate that caloric restriction, self-monitoring, and program attendance are more important than any specific composition of dietary macronutrient, results from a large European study indicated that weight-loss maintenance is better achieved with a diet modestly high in protein with lower glycemic index comparison to other macronutrient compositions. ^[122]

According to a study by Blüher et al, patients regaining weight after initial weight loss on long-term dietary intervention nevertheless continued to show long-lasting improvements in high-sensitivity C-reactive protein, adiponectin, fetuin, high-density lipoprotein cholesterol, progranulin, and vaspin. This finding may indicate that there are delayed effects following initial weight loss and/or continuous beneficial effects from switching to a healthier diet. ^[123]

Diet-induced weight loss can result in elevated levels of hormones that increase appetite. After successful weight loss, circulating levels of these hormones do not decrease to levels recorded before diet-induced weight loss. Thus, long-term strategies are needed to prevent obesity relapse. ^[124]

Contrary to the original belief, however, weight loss after nonsurgical intervention can be maintained long-term. A study by Hamdy et al showed that patients with diabetes and obesity can maintain an average of 6.4% weight loss after 5 years of intensive lifestyle changes in real-world clinical practice. This study also found that patients who maintain 7% or greater weight loss after a year are more likely to maintain weight loss over the long-term. ^[125]

In cases of childhood obesity, ^{[126, 127, 128]} the goal is not to cause weight loss, but to reduce the rate of weight gain to fit normal growth curves. The basic principles of management include the following:

• Modifying diet

• Increasing appropriate physical activity and exercise

• Reducing time spent in sedentary activities - Eg, watching television

• Modifying behavior

Medication therapy may also be used in the management of pediatric obesity, but close monitoring and a combination of all the aforementioned modalities is required to achieve substantial and sustained weight loss. In addition to olistat, liraglutide and semaglutide are approved by the US Food and Drug Administration (FDA) for use as adjuncts for weight loss in adolescents who meet the criteria for obesity. ^{[129, 130]}   

Setmelanotide, a melanocortin-4 agonist, was approved by the FDA in November 2020 for patients aged 6 years or older for weight control in obesity caused by rare genetic conditions (eg, proopiomelanocortin [POMC], proprotein convertase subtilisin/kexin type 1 [PCSK1], leptin receptor [LEPR] deficiencies). ^{[131, 132]}

For a full discussion of childhood obesity management, see the Medscape Drugs & Diseases article Obesity in Children.

Achieving a caloric deficit is still the most important component in achieving sustained weight loss. However, the considerable variance in individual energy expenditures and compliance with calorie-deficient plans make it difficult to reliably predict how much weight an individual will lose.

Among the caveats is the fact that energy expenditure is related to body weight; about 22 kcal/kg of energy is required for basal maintenance of 1 kg of weight in a typical adult. Therefore, weight loss tends to reduce energy expenditure, dampening the effect of caloric deficits.

Because of their lowered energy expenditure, older subjects have increased difficulty in achieving sustained weight loss. The estimated reduction in energy expenditure is 100 kcal per decade after the age of 30 years. Presumably because of their greater lean mass proportions, men tend to lose more weight than women do when caloric deficits are similar. ^[133]

In addition, some researchers have recommended using correction factors for estimating energy expenditure in obese patients. ^{[134, 135]} In a retrospective cross-sectional study of 1,331 patients with a body mass index (BMI) of at least 25 kg/m², Wilms and colleagues found that calculating resting oxygen uptake with the widely used 1-MET (metabolic equivalent) value of 3.5 ml O₂/kg/min overestimates actual values by 17% to 39% in overweight to severely obese individuals. ^{[134, 135]}

All subjects underwent resting energy expenditure (REE) testing with indirect calorimetry and 652 subjects also performed a symptom-limited bicycle cardiopulmonary exercise test to determine maximal achievable METs. Mean REE was 2.47 ml O₂/kg/min in women and 2.62 ml O2/kg/min in men. MET-REE decreased significantly with increasing BMI, and the deviation of MET-REE values from the predicted 1-MET value of 3.5 ml O₂/kg/min progressively increased.

The researchers developed sex-specific MET correction factors for distinct BMI groups. During the bicycle test, women performed 4.4 MET-peak and men performed 4.7 MET-peak. After the correction factors were applied, MET-peak increased to 6.2 in women and 6.1 in men. ^{[134, 135]}

Conventional diets can be broadly classified into 2 categories: balanced, low-calorie diets (or reduced portion sizes) and diets with different macronutrient compositions. The latter include the following:

• Low-fat diets - Eg, the Ornish diet

• Low-carbohydrate diets - Eg, the Atkins diet

• Midlevel diets - Eg, the Zone diet, in which the 3 major macronutrients (fat, carbohydrate, protein) are eaten in similar proportions of 30-40%)

• Joslin Why WAIT diet for diabetic patients - 40-45% carbohydrates, 20-30% protein, less than 35% fat

Reduced ̶ portion size diets and balanced, low-calorie diets

Balanced, low-calorie diets and reduced ̶ portion size diets are the types that dietitians and other weight-management professionals most commonly prescribe. Although these diets are useful for short-term weight loss, none of them alone is associated with reliable, sustained weight loss.

These diets underlie most of the popular, commercial weight-loss programs, such as those advocated by Jenny Craig, Weight Watchers, Take Off Pounds Sensibly (TOPS), and Overeaters Anonymous (OA). The basic premise for people on these diets involves obtaining their detailed dietary inventory and using it to estimate their mean daily caloric intake.

A reasonable goal for the caloric deficit is based on the new goal for total daily calories. Meal plans are then devised to provide this total, divided among 3 or more meals throughout the day.

Reduced ̶ portion size diets

The meals may be based on regular, everyday foods. In such cases, strategies for effective reduction of portion sizes become central.

Alternatively, portion control can be achieved by participation in structured weight loss programs (eg, Jenny Craig, Nutrisystem) or by the purchase of products such as meal-replacement shakes, bars, prepackaged meals, and frozen entrees (eg, Slim-Fast, Glucerna, Lean Cuisine, Healthy Choice, Smart Ones). These have adequate amounts of the major macronutrients based on the food pyramid from the US Department of Agriculture and recommended daily allowances (RDAs). These sources also have adequate micronutrients and trace elements.

Alcohol, sodas, most fruit juices, and highly concentrated sweets are generally calorie dense and nutrient deficient (so-called empty calories). Consequently, these are generally prohibited or reduced to a minimum.

Low-calorie diets

Low-calorie diets involve reducing daily caloric intake by 500-1000 kcal/day, to a level of 800-1800 kcal/day. These diets are associated with a mean weight loss of 0.4-0.5 kg per week (1-2 lb/wk). In ideal settings, total loss can be 5-10% of starting weight (10-20 lb for a 200-lb person) over 3-6 months, occasionally higher if the individual is very successful.

With any low-calorie diet, maintaining an intake of protein with a high biologic value of 1-1.5 g/kg of adjusted body weight (adjusted body weight = ideal body weight + one quarter of the excess weight) is vital to preserve lean body mass. Reducing intake to less than 1200 kcal/day while keeping the percentage protein at 15% may lead to protein malnutrition and significant muscle mass loss. For example, for a person following a 1200 calorie diet and aiming to consume 25% protein, the goal should be 300 kcal/day of protein (75 g).

Major potential complications to watch for include the following:

• Vitamin deficiency

• Starvation ketosis

• Electrolyte derangements

• Cholelithiasis

Diets with different macronutrient compositions

Diets with different macronutrient compositions involve a caloric intake of greater than 1200 kcal/day. This type of diet is designed to reduce the caloric intake by 500-1000 kcal/day from the patient's current dietary intake.

The suggested composition used by the best-validated dietary programs is as follows:

• Protein intake of 0.8-1.5 g/kg of body weight (not to exceed 100 g/day)

• 10-30% of total calories from fat (preferably ≥90% as polyunsaturated fat and < 10% as saturated fat)

• Carbohydrate intake of 50 g/day or more

• Water intake of 1 L or more

• Adequate micronutrients and macronutrients based on the RDAs

Low-carbohydrate diets

Low-carbohydrate diets have become popular in the past few decades, with the Atkins diet being the most popular. The Atkins diet is a high-protein and/or high-fat, very-low-carbohydrate diet that induces ketosis. The very ̶ low-carbohydrate content is critical in inducing short-term weight loss in the first 2-4 weeks; this is largely the result of fluid mobilization.

Ketone bodies tend to be generated when an individual’s daily dietary carbohydrate intake is under 50 g, and sodium diuresis is forced, causing most of the short-term weight loss. No robust data about the safety or long-term effectiveness of this diet are available.

The premise of the diet is that caloric intake as protein is less prone to fat storage than is the equivalent caloric intake as carbohydrate; however, no physiologic data support this premise. Owing to the high fat content of such diets, low-density lipoprotein cholesterol (LDL-C) levels were found to be increased by at least 10% in 25% of patients who used this diet.

Data on the long-term effects of a high-protein diet in rodents cause concern. They indicate that these diets may be associated with a reduced life span and a predisposition to neoplasia.

In 2 randomized trials, weight loss with Atkins-type diets was compared with conventional low-fat or balanced calorie-deficit diets. ^{[136, 137]} Although the Atkins-type diet led to the greatest initial weight loss, weight loss became similar within 1 year. Adherence to this diet is poor; in those studies noted, the noncompliance rate in the Atkins-type group was close to 50%.

The South Beach diet is another low-carbohydrate diet. This program is more liberal in its carbohydrate allowance than the Atkins diet. In addition, the South Beach diet distinguishes between what are considered to be good and bad carbohydrates on the basis of their glycemic index.

Although the relevance and importance of the glycemic index is controversial, the diet encourages increased fiber intake, which is associated with lowered weight even when total caloric intake is relatively unchanged. Low glycemic index diets are better at helping to maintain weight loss than diets with a higher glycemic index; the same is true of diets with modestly increased protein intake, versus standard protein intake. ^[122]

Persons who decide to use a low-carbohydrate diet should choose heart-healthy sources of fat, including monounsaturated fats, polyunsaturated fats, and fats rich in omega 3 fatty acids, rather than saturated fat. Protein sources should be fish, nuts, legumes, and lean poultry rather than pork chops, steak, and mutton.

Comparison of diet programs

Dansinger and colleagues compared the Zone, Ornish, and Atkins diets to each other and to a typical balanced, calorie-restricted (Weight Watchers) diet and found them all to have a similar impact on weight. ^[138] The Ornish diet (a very ̶ low-fat diet) and the Atkins diet had the poorest compliance rates. At 1 year, the researchers observed no significant differences in weight loss among the 4 diets. Compliance and caloric deficits were more important predictors of weight loss and improvement in cardiovascular risk surrogates than was specific dietary composition.

A 2-year study found low-carbohydrate and low-fat diets to be equally efficacious in inducing weight loss. However, the study also found that a low-carbohydrate diet is associated with favorable changes in cardiovascular disease risk factors. ^[136] Nevertheless, better achievement of sustained weight loss is seen with low-fat diets than with low-carbohydrate diets, probably because of generally higher compliance.

Very-Low-Calorie Diets

Very–low-calorie diets (VLCDs) are best used in an established, comprehensive program. VLCDs involve reducing caloric intake to 800 kcal/day or less. When used in optimal settings, they can achieve a weight loss of 1.5-2.5 kg/wk (3.3-5.5 lb/wk), with a total loss of as much as 20 kg over 12 weeks. No good-quality evidence suggests that a daily calorie intake of less than 800 kcal/day achieves any additional weight loss in the long-term. ^[139]

VLCDs are associated with profound initial weight loss, much of which is from loss of lean mass in the first few weeks. However, this loss rapidly ceases, and weight-loss velocity then flattens. Such rapid weight loss is frequently followed with weight regain due to reduction in basal energy expenditure secondary to the loss of fat free mass.

Use special caution whenever VLCDs are prescribed to children, adolescents, or elderly patients. Use of VLCDs is contraindicated in the following settings:

• Pregnancy

• Protein-wasting states

• Clinically significant cardiac, renal, hepatic, psychiatric, or cerebrovascular disease

• Any other chronic disease

Although VLCDs are associated with notable short-term weight loss and improved blood pressure and glycemic control, they cannot be sustained for longer than 3-6 months. Compliance beyond a few weeks is poor, and close supervision is required to avoid mishaps.

Among the major complications to monitor are hair loss, skin thinning, hypothermia, cholelithiasis, and electrolyte derangement. VLCDs have little or no utility in long-term weight management and are probably best used as stopgap measures before bariatric surgery or a long-term, comprehensive weight-loss program in patients with very severe or morbid obesity and associated comorbidities (body mass index [BMI] ≥50).

Preoperative VLCDs have been postulated to decrease surgical risk by enhancing visualization during laparoscopic bariatric surgery. In a multicenter, randomized, controlled trial involving 298 morbidly obese patients who underwent gastric bypass surgery, van Nieuwenhove et al reported a significantly lower rate of intraoperative complications among those who had undergone a 14-day VLCD before the procedure. ^[140] In addition, the surgeons’ perceptions of the procedure’s difficulty was lower in the VLCD patients.

There were, however, no significant differences in operative time or intraoperative complications between the control and VLCD groups. ^[140]

Dennis et al found that in overweight and obese middle-aged and older adults on a hypocaloric diet, drinking water before each main meal aided weight loss. In 48 adults aged 55-75 years with a BMI of 25-40 kg/m², those who consumed 500 mL of water prior to each daily meal had a 44% greater decline in weight over 12 weeks than did individuals on a hypocaloric diet without premeal water consumption. ^[141]

Water drinking could assist weight loss in overweight children. Drinking 10 mL/kg of cold water could result in an additional weight loss of about 1.2 kg/y. This is achieved primarily through a water-induced increase in resting energy expenditure. ^[142]

Before prescribing an intensive exercise program, clinicians should screen patients for cardiovascular and respiratory adequacy. Any clinically significant anomalies found require full evaluation by appropriate specialist physicians, and only after these issues have been adequately managed and stabilized should the patient begin an active exercise program. ^[143] In contrast, patients starting a program of moderate exercise (eg, walking) do not require prescreening.

Aerobic isotonic exercise is of the greatest value for persons who are obese. The ultimate minimum goal should be to achieve 30-60 minutes of continuous aerobic exercise 5-7 times per week. Increased physical activity and exercise 300 min/week is associated with significant weight reduction and longer maintenance of the weight loss. ^[144]

Anaerobic isometric exercise, including resistance training, can be cautiously added as an adjunct after the aerobic goal described above is achieved. Resistance training is valuable in minimizing muscle mass loss and is particularly beneficial in patients with diabetes, as it increases glucose uptake by muscles.

Since approximately 27% of the diet-induced weight loss is from loss of muscle, the addition of exercise to caloric restriction is important. Studies have shown that muscle mass loss is reduced to approximately 13% of the total weight loss when diet and exercise are combined. ^[145]

Exercise also increases metabolic activity and reduces body fat. Although most patients may be unable to sustain enough regular exercise to achieve weight loss, consistent, moderate exercise is important in maintaining weight and in improving overall cardiorespiratory fitness. ^[146] Shorter bouts of exercise of around 10 minutes are associated with better adherence and more weight loss than are longer bouts of exercise.

A study by Goodpaster et al showed that patients with severe obesity who introduced exercise concurrently with or after dietary intervention had significant weight loss and modification of cardiometabolic risk factors. ^[147] Furthermore, a study by Hankinson et al indicated that benefits of exercise in young age may translate into benefits beyond, particularly in young women. ^[148] This information is useful for patients and physicians who may be discouraged by the patients’ initial inability to engage in exercise.

A study by Rejeski et al indicated that community weight-loss and physical activity programs can have a positive impact on mobility in elderly people who are overweight or obese and are in poor cardiovascular health. ^[149] In this study, participants with poorer mobility at baseline benefited the most from these interventions.

Behavioral modification for weight loss addresses learned behaviors that contribute to excessive food intake, poor dietary choices or habits, and sedentary activity habits. Although this approach can yield improved results, it is inherently challenging and time-consuming. ^[150]

Effecting behavioral change starts with taking a detailed inventory of the patient’s daily activities, in order to identify activities, cues, circumstances, and practices that favor nonmeal eating and snacking. A trained professional must then have an in-depth discussion with the patient to develop an individualized plan to change these practices. The effectiveness of this modality depends on a highly motivated patient and a dedicated counselor who is willing to maintain long-term follow-up. ^{[151, 152]}

A sufficient amount of sleep favorably impacts the maintenance of fat-free mass during times of decreased energy intake. In contrast, insufficient sleep undermines the body's ability to limit expansion of fat mass. A healthy sleep pattern is therefore important to harness weight loss benefits from other interventions. ^[153] Seven to 8 hours of sleep are optimal. Shorter (< 6 h) or longer (>9 h) sleep duration is associated with increased total body weight. Treatment of obstructive sleep apnea, if present, also helps in weight reduction.

Few medications are available for the treatment of obesity. Examples of FDA-approved drugs that may be considered for the long-term treatment of obesity include orlistat (Xenical, Alli), the combinations of phentermine and extended-release topiramate (Qsymia), and the fixed-dose combination of bupropion and naltrexone (Contrave). Generally, the medications approved by the US Food and Drug Administration (FDA) for obesity are intended for patients with a BMI of 30 kg/m² or more or of 27 kg/m² or more with a weight-related risk factor (eg, diabetes, hypertension). All are indicated as adjuncts to caloric restriction, increased physical activity, and behavior modification. Response to therapy should be evaluated by week 12. If a patient has not lost at least 5% of baseline body weight, stimulants should be discontinued, as it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment.

The FDA has issued a consumer alert about over-the-counter weight-loss pills that contain undeclared, active pharmaceutical ingredients. These products, which are promoted and sold on Web sites and in retail stores, may be marketed as “dietary supplements.” They have not been approved by the FDA, are illegal, and may be potentially harmful. ^[154] In April 2015, the FDA banned the use of the amphetaminelike stimulant (BMPEA) in supplements (sometimes labeled as acacia rigidula). ^[155]

Glucagonlike peptide-1 agonists

Glucagonlike peptide-1 (GLP-1) is a physiologic regulator of appetite and caloric intake, and the GLP-1 receptor is present in several areas of the brain involved in appetite regulation. 

Semaglutide (Wegovy)

In June 2021, the FDA approved the use of the GLP-1 receptor agonist semaglutide for weight loss, in a 2.4-mg/week subcutaneous dose. The drug is indicated as an adjunct to diet and exercise for adults with an initial BMI of 30 kg/m² or greater (obesity). It also indicated for BMI of 27 kg/m² or greater (overweight) in the presence of at least one weight-related comorbid condition (eg, hypertension, type 2 diabetes mellitus, dyslipidemia). The approval was based on four phase-3 clinical trials in the Semaglutide Treatment Effect in People With Obesity (STEP) program involving approximately 4500 patients. The STEP 1, 2, and 4 trials reported a 15-18% weight loss over 68 weeks in individuals with overweight or obesity who received the medication. ^{[156, 157, 158]}

Liraglutide (Saxenda)

Liraglutide is a GLP-1 analog. It is approved for chronic weight management as an adjunct to diet and exercise in adults with a BMI of 30 kg/m² or higher (obese) or adults with a BMI of 27 kg/m² or higher (overweight) who have at least 1 weight-related condition (eg, hypertension, type 2 diabetes, dyslipidemia). The dose for obesity differs from that of liraglutide (Victoza) that is used to treat diabetes. Saxenda is initiated at 0.6 mg SC once daily for 1 week, and is then increased by 0.6 mg/day in weekly intervals until a dose of 3 mg/day is achieved.

Approval was based on data from 3 clinical trials that included about 4800 obese and overweight patients with and without significant weight-related conditions. Results from a clinical trial that enrolled patients without diabetes or with diabetes showed that patients had an average weight loss of 4.5% and 3.7% from baseline respectively compared to treatment with a placebo at 1 year. Of those treated with liraglutide, 62% of persons without diabetes and 49% of persons with diabetes lost at least 5% of their body weight compared with 34% or 16% treated with placebo, respectively. ^[159]  

Orlistat

Orlistat blocks the action of pancreatic lipase, reducing triglyceride digestion and, thus, absorption. Two major clinical trials showed sustained weight loss of 9-10% over 2 years. ^[160] Orlistat’s effectiveness in producing weight loss does not depend on systemic absorption. The drug may reduce absorption of some fat-soluble vitamins (A, D, E, K) and beta-carotene, as well as absorption of some medications. Adverse effects include flatulence, fatty/oily stool, increased defecation, and fecal incontinence.

Lorcaserin

On February 13, 2020, the FDA requested that lorcaserin be voluntarily withdrawn from the market by its manufacturer owing to a clinical trial indicating that the drug carries an increased cancer risk. For more information, see the FDA Drug Safety Communication. ^[161]

Lorcaserin was approved by the FDA in June 2012 as an adjunct to a reduced-calorie diet and exercise for long-term weight management in individuals with an initial BMI of 30 kg/m² or higher (obese) or 27 kg/m² or higher (overweight) with at least 1 weight-related comorbid condition (eg, hypertension, dyslipidemia, type 2 diabetes mellitus). ^[162] Lorcaserin is a schedule IV substance, since it has potential for abuse. ^[163]

Lorcaserin is thought to decrease food consumption and promote satiety by selectively activating 5-HT2C receptors on anorexigenic pro-opiomelanocortin neurons in the hypothalamus. Approval of lorcaserin was based on 3 double-blind, randomized, placebo-controlled trials that found lorcaserin (along with diet and exercise) to be more effective than diet and exercise alone at helping patients lose 5% or more of their body weight after 1 year and managing the weight loss for up to 2 years. ^{[164, 165, 166]}

Required postmarketing studies of lorcaserin will include a long-term trial to assess the risk for major adverse cardiac events. Lorcaserin should be used with caution in patients with heart failure, and it has not been studied in patients with serious valvular heart disease. ^[162]

Liraglutide (Saxenda)

Liraglutide is a glucagonlike peptide-1 (GLP-1) analog. GLP-1 is a physiological regulator of appetite and calorie intake, and the GLP-1 receptor is present in several areas of the brain involved in appetite regulation.

Liraglutide is approved for chronic weight management as an adjunct to diet and exercise in adults with a BMI of 30 kg/m² or higher (obese) or adults with a BMI of 27 kg/m² or higher (overweight) who have at least 1 weight-related condition (eg, hypertension, type 2 diabetes, dyslipidemia). The dose for obesity differs from that of liraglutide (Victoza) that is used to treat diabetes. Saxenda is initiated at 0.6 mg SC once daily for 1 week, and is then increased by 0.6 mg/day in weekly intervals until a dose of 3 mg/day is achieved.

Approval was based on data from 3 clinical trials that included about 4800 obese and overweight patients with and without significant weight-related conditions. Results from a clinical trial that enrolled patients without diabetes or with diabetes showed that patients had an average weight loss of 4.5% and 3.7% from baseline respectively compared to treatment with a placebo at 1 year. Of those treated with liraglutide, 62% of persons without diabetes and 49% of persons with diabetes lost at least 5% of their body weight compared with 34% or 16% treated with placebo, respectively. ^[159]  

Setmelanotide

Setmelanotide (Imcivree) is a melanocortin-4 agonist. It was approved by the FDA in November 2020 for patients aged 6 years or older for weight control in obesity caused by rare genetic conditions (eg, proopiomelanocortin [POMC], proprotein convertase subtilisin/kexin type 1 [PCSK1], leptin receptor [LEPR] deficiencies).  

Phase 3 clinical trials observed, after about 1 year of treatment, weight loss of at least 10% in 80% of patients with obesity caused by POMC or PCSK1 deficiency and in 45.5% of patients with obesity due to LEPR deficiency. Additionally, improvement was seen in hunger scores from baseline to 1 year. ^{[131, 132]}  

Phentermine and topiramate

The combination of phentermine and extended-release topiramate (Qsymia) was approved by the FDA in July 2012 as an adjunct to a reduced-calorie diet and exercise for long-term weight management in individuals with an initial BMI of 30 kg/m² or higher (obese) or 27 kg/m² or higher (overweight) with at least one weight-related comorbid condition (eg, hypertension, dyslipidemia, type 2 diabetes mellitus). ^[167] Use during pregnancy is contraindicated.

Topiramate, which was first licensed as an adjunctive antiepileptic agent, has been associated with profound weight loss (an average of 5-7% of initial weight). The amount of weight loss appears to be greater with higher baseline weights. The exact mechanism of this effect is being actively investigated. Although the degree of efficacy is exciting, the propensity for adverse effects, especially CNS effects such as drowsiness, paresthesias, memory loss, and confusion, is cause for concern.

This combination drug contains an extended-release form of topiramate. In addition, the dose of topiramate in this product (46 mg, although a 92-mg dose form is available for select patients) is lower than those used for seizure management (usually 200 mg twice daily).

Bupropion and naltrexone

This combination is thought to cause a reduction in appetite and increase in energy expenditure by increasing the activity of pro-opiomelanocortin (POMC) neurons. Bupropion increases dopamine activity in the brain, which appears to lead to a reduction in appetite and increase in energy expenditure by increasing activity of POMC neurons. Naltrexone blocks opioid receptors on the POMC neurons, preventing feedback inhibition of these neurons and further increasing POMC activity.

The combination is taken once daily initially, and the dose is gradually increased each week until two tablets are taken twice daily by week 4.

Drugs for short-term treatment

Four agents are available in the United States for short-term (8-12 weeks) treatment of obesity: diethylpropion, phendimetrazine, benzphetamine, and phentermine. Any of these drugs may be used as an adjunct in a regimen of weight reduction based on caloric restriction in patients with an initial BMI of 30 kg/m² or higher who have not responded to an appropriate weight-reducing regimen.

Medications used off-label

Several medications that are approved for other indications but that may also promote weight loss have been used off-label for obesity. These include several antidepressants, such as selective serotonin reuptake inhibitors (SSRIs). Medications used off-label for obesity include the following:

• Methylphenidate - Not approved by the FDA for obesity management, but several anecdotal reports have described it as having variable success for this purpose ^[168]

• Zonisamide - Gadde and colleagues reported that randomized use of the antiepileptic drug zonisamide in a cohort of 60 obese subjects was associated with a weight loss of about 6% of baseline weight, with few adverse effects ^[169]

• Octreotide - Lustig and colleagues reported the potential utility of octreotide in ameliorating the distinct subclass of hypothalamic obesity ^[170]

Diabetes medications

Metformin does not have an indication for obesity, but it is useful in preventing diabetes and improving insulin resistance in conditions such as polycystic ovary syndrome. Its use was associated with weight neutrality or mild weight loss. ^[171]

The first glucagonlike peptide (GLP)-1 analogue, exenatide (Byetta), although not FDA approved for obesity management, has been associated with modest weight loss in subjects with type 2 diabetes. A similar effect was seen with liraglutide (Victoza) and long-acting exenatide (Bydureon), which also are not approved by the FDA for obesity management. Higher liraglutide doses of 2.4 mg and 3 mg/day were found to be significantly more effective than orlistat for the management of obesity in nondiabetic patients. The FDA approved liraglutide (Saxenda) for obesity in December 2014 (see above).

A systematic review and meta-analysis by Vilsbøll et al found that treatment with GLP-1 receptor agonists results in weight loss among overweight or obese patients with or without type 2 diabetes. ^[172] GLP-1 agonist regimens reviewed included exenatide twice daily, exenatide once weekly, and liraglutide once daily at clinically relevant doses for at least 20 weeks.

Antidepressants

Although not all are FDA approved for this purpose, several SSRIs may cause anorexia as one of their major adverse effects. Some of these medications have been used as adjuncts in the medical management of obesity, with variable success. A meta-analysis of antidepressants and body weight found that fluoxetine was associated with some weight loss, although this effect appeared to be limited to the acute phase of treatment. ^[167]

Bupropion is licensed for use as an antidepressant and for use in smoking cessation. It is associated with minimal to moderate weight loss in obese patients. ^[173] A combination of bupropion and naltrexone (Contrave) was approved on September 10, 2014 for use as adjunct to a reduced-calorie diet and increased physical activity for long-term weight management in adults with initial body mass index of 30 kg/m² (obese) or ≥27 kg/m² (overweight) in presence of at least one weight-related comorbidity (eg, hypertension, type 2 diabetes, or dyslipidemia).

Ephedrine and caffeine

Ephedrine and caffeine are second-line options in the medical management of obesity. They both act by increasing energy expenditure, but they are associated with the potential for tachycardia, hypertension, and palpitations. These medications are associated with greater weight loss when used in combination than when used alone. They cause 25-40% of their weight loss by inducing thermogenesis, but they also decrease food intake, which accounts for 60-75% of the weight-loss effect.

Currently, the evidence for the efficacy of these 2 drugs in promoting weight loss is inconclusive. Neither substance has an FDA-approved indication for the treatment of obesity.

Cannabinoid-receptor antagonists

The central cannabinoid system has an increasingly recognized role in appetite and feeding disorders. ^{[174, 175, 176, 177]} In particular, activation of the cannabinoid type 1 (CB1) receptor is associated with increased appetite and appears to be the basis for the effectiveness of dronabinol in enhancing diet in patients with acquired immunodeficiency syndrome (AIDS) and other wasting syndromes.

CB1-receptor antagonists showed great potential for weight management in several human trials. Rimonabant, the most-developed CB1-receptor antagonist, caused a mean weight loss of 3-6 kg over a 1-year follow-up at doses of 5-20 mg/day. Adverse effects, which were most prevalent at high doses, included dizziness, depression and suicidal ideation, headaches, nausea, vomiting, and diarrhea. The drug was rejected by the FDA because of side effects of depression and suicidal ideation; in Europe, it was approved but later recalled.

Catechin

A Japanese study found evidence that beverages containing high amounts of catechin, a flavonoid found in green tea, may aid in preventing obesity. ^[178] Patients in the investigation, all of whom had type 2 diabetes mellitus, ingested either 582.8 mg or 96.3 mg of catechins per day by drinking green tea. By the 12th week, participants receiving the higher catechin dose had undergone a significantly greater reduction in waist circumference than did patients receiving the lower dose.

Other potential antiobesity agents

The increasing knowledge that has come on the heels of the discovery of leptin by Friedman and colleagues in 1994 has spurred a whirlwind of research that has identified several potential pharmaceuticals. However, safety standards for obesity medications are necessarily high. Tolerance for adverse effects is limited; most persons who are obese are fairly healthy in the short term, but the risk for adverse drug effects is enhanced because patients must take antiobesity medications for extended periods (possibly for the rest of their lives).

Agents in early phases of investigation that may yet prove useful against obesity include the following:

• Ghrelin antagonists,

• Alpha–melanocyte-stimulating hormone analogs

• Enterostatin

• Neuropeptide YY antagonists

• Beta3-adrenergic agonists

In addition, various nutraceuticals and herbal products have shown promise. For example, an extract from the African cactus Hoodia gordonii may cause clinically significant appetite suppression.

The diabetes drug pramlintide (Symlin), which is a synthetic analogue of the pancreatic hormone amylin, does not have an FDA indication for obesity management. However, this drug is clearly associated with variable weight loss in people with type 1 or 2 diabetes, while improving overall glycemic control. Higher doses (240 mcg before main meals) than those approved for the management of type 2 diabetes (60-120 mcg before main meals) have produced modest weight loss in obese or overweight patients with and without diabetes. ^[179]

Peptide YY (3-36) is being developed as a nasal inhaler. Ongoing, preliminary phase 1 and 2 trials yielded encouraging results. ^{[180, 181, 182]}

Leptin is still used in cases of the rare obesity subclass of leptin-deficient obesity and lipodystrophy, but a study of the leptin analogue metreleptin in obese patients with diabetes found that metreleptin did not alter body weight. ^[183] The combination of metreleptin with pramlintide, however, led to enhanced weight loss in one study, ^[184] but a more recent randomized clinical trial on the combination of these 2 drugs was stopped because of safety concerns. ^[185]

Preliminary reports suggest the potential utility of agents that impede dietary carbohydrate absorption. Tagatose is one of the compounds in this class that is undergoing trials.

Drugs no longer used or efficacy not proven

The history of obesity medications is replete with disasters that have taught caution in the use of this group of medicines. For example, among the initial medications used for obesity management were amphetamine, methamphetamine, and phenmetrazine. These were all withdrawn because of their high potential for abuse.

The combination of fenfluramine and phentermine (“fen-phen”) was used in some long-term trials with excellent results. However, fenfluramine was withdrawn in 1997 (along with D-fenfluramine) because of the potential for adverse cardiac, valvular, and pulmonary hypertensive effects in patients taking this drug.

Other former antiobesity medications, and the reasons for their abandonment, include the following:

• Thyroid hormone - Hyperthyroidism, with its attendant sequelae

• Dinitrophenol - Cataracts and neuropathy

• Rainbow pills (a mixture of digitalis and diuretics) - Fatal arrhythmias and electrolyte derangements

• Aminorex - Pulmonary hypertension

• Phenylpropanolamine - Increased risk of myocardial infarction and stroke

Other drugs withdrawn from the US market include benzphetamine and mazindol.

Some agents that initially showed promise were later demonstrated to be poor prospects in rigorous randomized intervention trials. These include the following:

• Guar gum

• Chitosan

• Axokine - Or ciliary neurotrophic factor, the use of which was associated with the development of autoantibodies and marked reduction in anorexiant potency in about 30% of subjects

• St. John's wort

• Psyllium

• Conjugated linoleic acid

• Chromium

• Ginseng

One strategy to prevent obesity that is being explored in the dietary industry involves the use of fat substitutes. Olestra (Olean) has been approved for use as a dietary supplement and additive in various foods, such as potato chips and crackers. Olestra has a calorie value of 0 kcal/g, whereas fat has a value of approximately 9.1 kcal/g. Olestra consists of a sucrose polyester backbone with 6-8 fatty-acid side chains; this structure makes the molecule too large for digestive enzymes of the gut to hydrolyze.

In many trials, olestra had fairly good tolerability, although foods containing it are apparently less tasty than foods cooked in regular fat. The major adverse effects reported were flatulence, bloating, diarrhea, and loose stools. Because of concerns regarding the possible malabsorption of fat-soluble vitamins, the FDA requires all olestra-prepared foods to be supplemented with these vitamins.

Two margarines, Benecol and Take Control, block cholesterol absorption in the intestine and can lower total and LDL-cholesterol levels 10% and 13-15%, respectively. Benecol contains stanols, predominantly sitostanol and campestan; Take Control is made up of sterols, primarily beta-sitosterol and campesterol. Weight-loss benefits have not been demonstrated.

Surgical therapy for obesity (bariatric surgery) is the only available therapeutic modality associated with clinically significant and relatively sustained weight loss in subjects with morbid obesity associated with comorbidities. Evidence shows that well-performed bariatric surgery, in carefully selected patients and with a good multidisciplinary support team, substantially ameliorates the morbidities associated with severe obesity.

Although bariatric surgery is the only therapeutic method associated with significant and rapid weight loss, it is expensive, highly procedure and surgeon specific, and certainly not the solution for the burgeoning obesity epidemic. Patient selection for bariatric procedures must be addressed along the same stringent lines as those discussed earlier for the selection of patients for medical weight-management programs.

The standard criteria for bariatric surgery have stated that at a minimum, patients should be considered candidates for bariatric procedures only if they have a BMI of greater than 40 kg/m² and/or a weight greater than 45 kg above the age- and sex-defined ideal weight. For subjects with BMIs of 35-40 kg/m², at least 1 major comorbidity had to be present to justify these procedures. ^{[114, 115]}  (The presence of comorbidities is not a contraindication to bariatric surgical procedures; however, the patient's condition must be stabilized and adequately treated before surgery.)

However, guidelines published in 2022 by the American Society for Metabolic and Bariatric Surgery (ASMBS) and the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) revised the criteria for bariatric surgery. The groups’ joint guidelines state the following ^[186] :

• It is recommended that individuals with a BMI ≥35 kg/m ² undergo metabolic and bariatric surgery (MBS), regardless of the severity of comorbidities or whether or not any exist
• Persons with metabolic disease and a BMI of 30-34.9 kg/m ² should be considered for MBS
• In the Asian population, BMI thresholds should be adjusted so that BMIs ≥25 kg/m ² and ≥27.5 kg/m ² suggest clinical obesity and engender an offer of MBS, respectively
• MBS should be considered in appropriately selected children and adolescents

Comorbidities that have been reported to be improved, ameliorated, or resolved through bariatric surgery include the following:

• Obstructive sleep apnea

• Type 2 diabetes mellitus

• Hypertension

• Heart failure

• Peripheral edema

• Respiratory insufficiency

• Asthma

• Dyslipidemia

• Esophagitis

• Pseudotumor cerebri

• Operative risk

• Osteoarthritis

• Thromboembolism

• Urinary incontinence

Other reports suggest improved quality of life and fertility after bariatric surgery. Although other outcomes are difficult to demonstrate and are awaiting clear documentation, these procedures may substantially reduce macrovascular complications (eg, myocardial infarction), stroke, amputations, obesity-related malignancies, and a predisposition to infection, hernias, and varicose veins. ^[187]

Although most bariatric procedures were initially developed in the setting of laparotomies, they now are increasingly performed laparoscopically, with reduced postoperative morbidity. The laparoscopic approach to bariatric surgery is particularly well developed in Europe.

Among the standard bariatric procedures are the following:

• Roux-en-Y gastric bypass

• Adjustable gastric banding

• Gastric sleeve surgery

• Vertical sleeve gastrectomy

• Horizontal gastroplasty

• Vertical banded gastroplasty

• Duodenal-switch procedures

• Biliopancreatic bypass

• Biliopancreatic diversion

Available data on the effectiveness of many of these procedures are still relatively scant. However, reports and meta-analyses from large numbers of patients on the most commonly performed procedures (gastric restriction and gastric bypass) lend veracity to the long-term effectiveness of bariatric surgery. ^{[89, 188, 189]}

Guidelines from the American Association of Clinical Endocrinologists, The Obesity Society, and the American Society for Metabolic and Bariatric Surgery endorse sleeve gastrectomy as an effective alternative to gastric banding, gastric bypass, and other types of bariatric surgery, saying that the procedure has advanced beyond the investigational stage. However, the guidelines do not recommend any bariatric procedure as preferable over the others for patients with severe obesity. ^{[190, 191, 192]}

Vertical-banded gastroplasty

Ashley and colleagues, in an evaluation of 114 patients who underwent vertical-banded gastroplasty, found that about 60% of them lost more than 50% of their excess body weight over 1 year. ^[193] No patient lost less than 25%, and within a year of the surgery, mean BMI had decreased from 44.8 to 32.5 kg/m².

Gastric bypass

Flickinger and associates, in an examination of 210 patients who received a Roux-en-Y gastric bypass, recorded a mean weight loss of 51 kg in 18 months, which was then maintained over 36 months of follow-up. ^[194] Only 4% of the patients required a repeat operation. Sugerman and colleagues reported that, among patients undergoing gastric bypass, two thirds of their excess body weight was lost over 2 years, 60% of the excess body-weight loss was maintained at 5 years, and more than 50% of excess body-weight loss was maintained at 8-9 years’ follow-up. ^[23]

Roux-en-Y and other gastric-bypass procedures generally result in more weight loss than do gastric-restriction procedures. When 329 patients receiving vertical gastroplasty procedures were compared with 623 persons undergoing Roux-en-Y gastric bypass, weight loss was maintained in 47% and 62% of patients, respectively, over 5-9 years of follow-up. ^[23]

According to a study by Plecka et al, in patients who are morbidly obese, gastric bypass (but not restrictive surgery) apparently reduces the risk levels for the development of type 2 diabetes and myocardial infarction to those for the general population. However, the mortality risk in these patients nonetheless remains higher than that in the general population. ^[195]

Mingrone et al reported regression of diabetes (defined as fasting glucose < 100 mg/dL and hemoglobin A1c [HbA1c] < 6.5% in the absence of pharmacologic therapy) at 2 years in 75% of Roux-en-Y gastric bypass patients and 95% of biliopancreatic-diversion patients. ^[196] This randomized, controlled trial included 60 patients with a BMI of more than 35, a history of at least 5 years of type 2 diabetes, and HbA1c of 7% or greater. Improvement in glucose control was unrelated to baseline BMI or overall weight loss.

A Norwegian study compared gastric bypass with duodenal switch and determined that duodenal switch surgery was associated with greater weight loss and greater reductions in total and LDL-C levels. However, duodenal switch surgery was also associated with reductions in concentrations of vitamin A and 25-hydroxyvitamin D, as well as with increased adverse effects. ^[197]

Similarly, a randomized trial from Sweden found greater postoperative weight loss in patients who had duodenal switch surgery than in those who had gastric bypass. Fasting glucose and HgA1c were also lower at 3 years in the duodenal switch group. ^[198]

A study by Schiavon et al indicated that bariatric surgery can lead to a reduction in the number of antihypertensive drugs required by persons with obesity taking multiple blood pressure agents and in some cases can eliminate the need for any such medications. The study involved 96 patients with a BMI of 30 to just under 40 kg/m², including 49 who underwent laparoscopic Roux-en-Y gastric bypass and a control group of 47 treated only with medical and lifestyle therapy. The investigators found that 83.7% of the surgery group, but just 12.8% of the control patients, were able to reduce the total number of antihypertensive medications they were taking by at least 30%. Moreover, at 12 months, 51% of the surgery patients were able to maintain an office-measured blood pressure of under 140/90 mm Hg without any blood pressure drugs, a milestone that none of the control patients reached. ^{[199, 200]}

Gastric pacing

Emerging data suggest that gastric pacing achieved by using implantable electrodes may have significant weight-loss effects. This outcome was initially discovered with the use of gastric pacemaker devices for gastroparesis in patients with diabetes.

Cigaina reported that 10 patients in whom a pacing device was laparoscopically implanted showed a mean excess weight loss of about 25% at 3-year follow-up. ^[201] Similar findings were reported in several European studies with a total cohort of about 50 patients.

Other procedures

Other adjunctive procedures that may be performed but that have an unclear utility include visceral fat removal, omentectomy, subcutaneous fat panniculectomy, and large-volume subcutaneous fat liposuction. Klein and colleagues indicated that liposuction in itself has no utility in improving cardiac risk factors among patients with obesity. ^[202]

Some procedures, such as jaw wiring and insertion of a gastric balloon or a gastric wrap, are no longer popular because of their poor results compared with those of newer procedures and because of their high complication rates. Vagotomy has also declined in popularity, as the weight lost is typically regained within a few years. A few reports suggest that when vagotomy is performed with gastric bypass, it increases weight loss by as much as 20%, but this finding has not been consistently replicable.

Surgical complications

The mortality rate associated with standard bariatric surgical procedures in an experienced center should not exceed 1.5-2%. The surgical mortality rate is less than 0.5% at centers specializing in bariatric surgery. Mortality rates exceeding 2% suggest a risk-to-benefit ratio that probably is unacceptable.

Major procedure-specific postoperative complications include the following:

• Wound dehiscence

• Stomal strictures

• Erosions or ulcers

• Postprocedure diarrhea

• Malabsorption

• Nutritional and vitamin deficiency

• Dumping syndrome

• Anastomotic leaks with a potential for mediastinitis or peritonitis

In addition, gastric-specific operations can be associated with persistent vomiting and metabolic alkalosis. These operations are also more commonly associated with weight-loss failure and inadvertent splenectomy than are other surgical methods. Malabsorptive procedures (gastric bypass) can lead to deficiency of thiamine, iron, vitamin D, and vitamin B-12.

Gastric resection

Prevalences for adverse events with gastric resection procedures with or without bypass are approximately as follows ^[203] :

• Dumping - 70%

• Dairy intolerance - 50%

• Constipation - 40%

• Headaches – 40%

• Depression - 15%

• Hair loss - 33%

• Vitamin B-12 deficiency - 25%

• Incisional hernias, anemia, diarrhea, or abdominal pain - 15%

• Arrhythmias – 10%

• Single or multiple vitamin deficiencies not involving vitamin B-12 -10%

Malabsorptive procedures

Patients who receive bypass procedures are particularly prone to micronutrient deficiency states, especially of calcium, vitamin B-12, folate, and iron, as well as protein malnutrition.

Rare cases of postural hypotension and severe hypoglycemia from nesidioblastosis have been reported. Life-threatening hypoglycemia usually requires partial or total pancreatectomy, while severe postural hypotension that cannot be corrected with fludrocortisone and midodrine requires reversal of the surgery.

The following are among the major specific complications associated with malabsorptive operations:

• Uncontrolled diarrhea

• Steatorrhea

• Malabsorption of fat-soluble vitamins

• Potassium and/or magnesium deficiency

• Blind-loop syndrome - Includes enteritis, arthropathy, and liver cirrhosis

• Gallstone development

• Urolithiasis

• Metabolic encephalopathy

Failure rates

If failure is defined as an inability to ameliorate comorbidities or prevent their recurrence, gastric bypass appears to have a failure rate of approximately 20%. Failure rates based on weight loss are controversial.

The overall failure rates for malabsorptive procedures are relatively low, although the need for reversal of the surgery because of resulting adverse effects appears to be relatively high.

Follow-up studies

Despite the morbidity and mortality risk associated with bariatric surgery, the few reports involving follow-up on patients undergoing these procedures suggest overall improvement in quality of life. Even more convincing than this finding is that most subjects who undergo these procedures, despite their postoperative complications and difficulties, indicate that they would undergo the procedures again if necessary.

Inpatient evaluations of obese patients are important in the immediate postoperative period after antiobesity surgery. In addition, hospitalization may be required for the management of major complications, such as clinically significant respiratory or cardiac compromise.

Weight-management programs may be based in an outpatient or inpatient setting. No rigorous evidence suggests that inpatient programs are necessarily superior to outpatient programs of similar structure and content, however. Inpatient programs may offer the convenience of easy access to patients and ease of monitoring, but they are not only expensive to run and difficult to reimburse, they also generally cause considerable disruption to the patients' regular routine. In addition, they offer little guarantee of sustained effect.

Because of the sheer prevalence of obesity and the anticipated worsening of the pandemic in the next few decades, prevention is by far the most desirable means to curb the medical and economic consequences of this condition. However, few trials have addressed this issue, and those performed thus far have had mixed results. ^[148]

Given the global proportions of obesity, a concerted approach is needed to address the problem and should involve the development of a massive public health education program aimed at adults and children as a means of changing their eating, activity, and behavioral habits. Cooperative efforts will also be needed among public health authorities, caterers, the fast food industry, and organizers of sports and outdoor games.

Results of some public health education initiatives in Singapore and parts of China that are only now being evaluated suggest, as hoped, that such programs have the potential for reducing the incidence and prevalence of obesity and may also have an impact on the major comorbidities of obesity, such as type 2 diabetes and hypertension. Until advances in gene therapy permit the alteration of genes that predispose to obesity, such programs are the only preventive options available.

The following consultations are recommended in the treatment of obesity:

• Dietitians

• Exercise and physical therapists

• Behavioral scientists and/or psychologists

• Bariatric surgeon - In appropriate setting

In select cases, consultation with a psychiatrist may be indicated. Psychiatric consultation should be sought for patients with psychiatric disorders and personality disorders (eg, severe depression, mania, obsessive disorders) that may be worsened by attempts at weight loss if not adequately treated and controlled

As with the management of other chronic medical conditions (eg, diabetes mellitus, hypertension, bronchial asthma), long-term success in the management of obesity is contingent on long-standing follow-up with the weight-loss program. Experience obtained from the lifestyle intervention group of patients in the Diabetes Prevention Program and information drawn from the ongoing Diabetes Prevention Program Observation study have borne out the importance of regular follow-up.

Patient visits may not need to occur as frequently during follow-up as during the initial weight-loss phase. Nevertheless, they are paramount if the lessons learned regarding diet, exercise habits, and behavioral patterns are to be maintained.