Obesity Treatment & Management
- Author: Osama Hamdy, MD, PhD; Chief Editor: Romesh Khardori, MD, PhD, FACP more...
Treatment of obesity starts with comprehensive lifestyle management (ie, diet, physical activity, behavior modification), which should include the following :
Self-monitoring of caloric intake and physical activity
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.[77, 78]
In January, 2015, the Endocrine Society released new guidelines on the treatment of obesity to include the following:[79, 80]
Diet, exercise, and behavioral modification should be included in all obesity management approaches for body mass index (BMI) of 25 kg/m 2 or higher. Other tools, such as pharmacotherapy for BMI of 27 kg/m 2 or higher with comorbidity or BMI over 30 kg/m2 and bariatric surgery for BMI of 35 kg/m 2 with comorbidity or BMI over 40 kg/m 2, 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/m 2 or higher or in individuals with a BME of 27 kg/m 2 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 glucagon-like 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 BMI of more than 27 kg/m 2 with comorbidities or BMI of more than 30 kg/m 2 seeking contraception, oral contraceptives are suggested over injectable medications because of weight gain with injectables, provided that women are well informed about risks and benefits (ie, oral contraceptives are not contraindicated).
The 3 major phases of any successful weight-loss program are as follows:
Preinclusion screening 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.
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.
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.
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.[77, 78]
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:
Electrolyte derangements - Hypokalemia is the most important of these
Psychological sequelae - Including depression and the development of eating disorders (particularly binge-eating disorders)
Patient Screening, Assessment, and Expectations
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.
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. 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%.[77, 78]
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.
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
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.
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.
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.
Treatment of Childhood Obesity
In cases of childhood obesity,[87, 88, 89] 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:
Increasing appropriate physical activity and exercise
Reducing time spent in sedentary activities - Eg, watching television
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. At the present, orlistat is the only medication approved by the US Food and Drug Administration (FDA) for use as an adjunct for weight loss in adolescents.
For full discussion of this topic, see the Medscape Reference article Obesity in Children.
Energy Expenditure and Weight Loss
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.
In addition, some researchers have recommended using correction factors for estimating energy expenditure in obese patients.[91, 92] 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.[91, 92]
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.[91, 92]
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 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:
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 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.[93, 94] 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.
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. 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. 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 (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.
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:
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. 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.
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.
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.
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. 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.
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.
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. 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. Furthermore, a study by Hankinson et al indicated that benefits of exercise in young age may translate into benefits beyond, particularly in young women. 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. 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.
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.[109, 110]
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. 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. At present, the only FDA-approved drugs for the long-term treatment of obesity are orlistat (Xenical), lorcaserin (Belviq), and the combination of phentermine and extended-release topiramate (Qsymia).
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. In April 2015, the FDA banned the use of the amphetaminelike stimulant (BMPEA) in supplements (sometimes labeled as acacia rigidula).
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. 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 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). Lorcaserin is a schedule IV substance, since it has potential for abuse.
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.[117, 118, 119]
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.
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 (obese) or adults with a BMI of ≥27 (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 4,800 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.
Phentermine and topiramate
The combination of phentermine and extended-release topiramate 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 1 weight-related comorbid condition (eg, hypertension, dyslipidemia, type 2 diabetes mellitus). 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.
Qsymia 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).
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 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 
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 
Octreotide - Lustig and colleagues reported the potential utility of octreotide in ameliorating the distinct subclass of hypothalamic obesity 
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.
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. 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.
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.
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. 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.
The central cannabinoid system has an increasingly recognized role in appetite and feeding disorders.[129, 130, 131, 132] 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.
A Japanese study found evidence that beverages containing high amounts of catechin, a flavonoid found in green tea, may aid in preventing obesity. 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:
Alpha–melanocyte-stimulating hormone analogs
Neuropeptide YY antagonists
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.
Peptide YY (3-36) is being developed as a nasal inhaler. Ongoing, preliminary phase 1 and 2 trials yielded encouraging results.[135, 136, 137]
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. The combination of metreleptin with pramlintide, however, led to enhanced weight loss in one study, but a more recent randomized clinical trial on the combination of these 2 drugs was stopped because of safety concerns.
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 phendimetrazine, 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:
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
Conjugated linoleic acid
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.
At a minimum, patients should be considered candidates for these 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 must be present to justify these procedures.[77, 78] 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.
Comorbidities that have been reported to be improved, ameliorated, or resolved through bariatric surgery include the following:
Obstructive sleep apnea
Type 2 diabetes mellitus
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.
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
Vertical banded gastroplasty
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.[57, 142, 143]
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.[144, 145, 146]
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. 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.
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. 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.
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.
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.
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. 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.
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.
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. Similar findings were reported in several European studies with a total cohort of about 50 patients.
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.
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.
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:
Erosions or ulcers
Nutritional and vitamin deficiency
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.
Prevalences for adverse events with gastric resection procedures with or without bypass are approximately as follows :
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%
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:
Malabsorption of fat-soluble vitamins
Potassium and/or magnesium deficiency
Blind-loop syndrome - Includes enteritis, arthropathy, and liver cirrhosis
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.
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.
Deterrence and Prevention
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.
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:
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.
Roundtable on Obesity Solutions, Food and Nutrition Board, Health and Medicine Division, National Academies of Sciences, Engineering, and Medicine. Obesity in the Early Childhood Years: State of the Science and Implementation of Promising Solutions: Workshop Summary. 2016 May 23. Available at http://www.ncbi.nlm.nih.gov/books/NBK368372/.
Flegal KM, Carroll MD, Kit BK, Ogden CL. Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010. JAMA. 2012 Feb 1. 307(5):491-7. [Medline].
Wijga AH, Scholtens S, Bemelmans WJ, de Jongste JC, Kerkhof M, Schipper M, et al. Comorbidities of obesity in school children: a cross-sectional study in the PIAMA birth cohort. BMC Public Health. 2010 Apr 9. 10:184. [Medline]. [Full Text].
Li C, Ford ES, Zhao G, Croft JB, Balluz LS, Mokdad AH. Prevalence of self-reported clinically diagnosed sleep apnea according to obesity status in men and women: National Health and Nutrition Examination Survey, 2005-2006. Prev Med. 2010 Jul. 51(1):18-23. [Medline].
Jiao L, Berrington de Gonzalez A, Hartge P, Pfeiffer RM, Park Y, Freedman DM, et al. Body mass index, effect modifiers, and risk of pancreatic cancer: a pooled study of seven prospective cohorts. Cancer Causes Control. 2010 Aug. 21(8):1305-14. [Medline]. [Full Text].
Oreopoulos A, Padwal R, McAlister FA, Ezekowitz J, Sharma AM, Kalantar-Zadeh K, et al. Association between obesity and health-related quality of life in patients with coronary artery disease. Int J Obes (Lond). 2010 Sep. 34(9):1434-41. [Medline].
Galtier-Dereure F, Boegner C, Bringer J. Obesity and pregnancy: complications and cost. Am J Clin Nutr. 2000 May. 71(5 Suppl):1242S-8S. [Medline].
Wadden TA, Webb VL, Moran CH, Bailer BA. Lifestyle modification for obesity: new developments in diet, physical activity, and behavior therapy. Circulation. 2012 Mar 6. 125(9):1157-70. [Medline]. [Full Text].
Cawley J, Meyerhoefer C. The medical care costs of obesity: an instrumental variables approach. J Health Econ. 2012 Jan. 31(1):219-30. [Medline].
Finkelstein EA, DiBonaventura Md, Burgess SM, Hale BC. The costs of obesity in the workplace. J Occup Environ Med. 2010 Oct. 52(10):971-6. [Medline].
Weight Loss Markets for Products and Services. BCC Research. Available at http://www.bccresearch.com/report/weight-loss-markets-products-services-fod027c.html. Accessed: April 23, 2012.
Gallagher D, Heymsfield SB, Heo M, Jebb SA, Murgatroyd PR, Sakamoto Y. Healthy percentage body fat ranges: an approach for developing guidelines based on body mass index. Am J Clin Nutr. 2000 Sep. 72(3):694-701. [Medline].
Ward LC. Segmental bioelectrical impedance analysis: an update. Curr Opin Clin Nutr Metab Care. 2012 Sep. 15(5):424-9. [Medline].
Shiwaku K, Anuurad E, Enkhmaa B, Kitajima K, Yamane Y. Appropriate BMI for Asian populations. Lancet. 2004 Mar 27. 363(9414):1077. [Medline].
Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C. Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation. 2004 Jan 27. 109(3):433-8. [Medline]. [Full Text].
Tan CE, Ma S, Wai D, Chew SK, Tai ES. Can we apply the National Cholesterol Education Program Adult Treatment Panel definition of the metabolic syndrome to Asians?. Diabetes Care. 2004 May. 27(5):1182-6. [Medline]. [Full Text].
Tirosh A, Shai I, Afek A, Dubnov-Raz G, Ayalon N, Gordon B, et al. Adolescent BMI trajectory and risk of diabetes versus coronary disease. N Engl J Med. 2011 Apr 7. 364(14):1315-25. [Medline].
Montonen J, Boeing H, Schleicher E, Fritsche A, Pischon T. Association of changes in body mass index during earlier adulthood and later adulthood with circulating obesity biomarker concentrations in middle-aged men and women. Diabetologia. 2011 Jul. 54(7):1676-83. [Medline].
Sugerman HJ, Kellum JM, Engle KM, Wolfe L, Starkey JV, Birkenhauer R, et al. Gastric bypass for treating severe obesity. Am J Clin Nutr. 1992 Feb. 55(2 Suppl):560S-566S. [Medline].
Sugerman HJ. Effects of increased intra-abdominal pressure in severe obesity. Surg Clin North Am. 2001 Oct. 81(5):1063-75, vi. [Medline].
Yao R, Ananth CV, Park BY, Pereira L, Plante LA, for the Perinatal Research Consortium. Obesity and the risk of stillbirth: a population-based cohort study [abstract]. Presented at: The 2014 SMFM Annual Meeting; February 3-8, 2014; New Orleans, LA. Am J Obstet Gynecol. 2014. 210:[Full Text].
Hackethal V. Obese women may have 25% increased risk for stillbirth. Medscape Medical News. March 27, 2014. [Full Text].
Abdullah A, Amin FA, Hanum F, et al. Estimating the risk of type-2 diabetes using obese-years in a contemporary population of the Framingham Study. Glob Health Action. 2016. 9:30421. [Medline].
Losina E, Walensky RP, Reichmann WM, Holt HL, Gerlovin H, Solomon DH, et al. Impact of obesity and knee osteoarthritis on morbidity and mortality in older Americans. Ann Intern Med. 2011 Feb 15. 154(4):217-26. [Medline].
Adelman RD, Restaino IG, Alon US, Blowey DL. Proteinuria and focal segmental glomerulosclerosis in severely obese adolescents. J Pediatr. 2001 Apr. 138(4):481-5. [Medline].
Kasiske BL, Napier J. Glomerular sclerosis in patients with massive obesity. Am J Nephrol. 1985. 5(1):45-50. [Medline].
Jennette JC, Charles L, Grubb W. Glomerulomegaly and focal segmental glomerulosclerosis associated with obesity and sleep-apnea syndrome. Am J Kidney Dis. 1987 Dec. 10(6):470-2. [Medline].
Hairston KG, Bryer-Ash M, Norris JM, Haffner S, Bowden DW, Wagenknecht LE. Sleep duration and five-year abdominal fat accumulation in a minority cohort: the IRAS family study. Sleep. 2010 Mar. 33(3):289-95. [Medline]. [Full Text].
Spiegel K, Tasali E, Penev P, Van Cauter E. Brief communication: Sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite. Ann Intern Med. 2004 Dec 7. 141(11):846-50. [Medline].
Martinelli CE, Keogh JM, Greenfield JR, Henning E, van der Klaauw AA, Blackwood A, et al. Obesity due to melanocortin 4 receptor (MC4R) deficiency is associated with increased linear growth and final height, fasting hyperinsulinemia, and incompletely suppressed growth hormone secretion. J Clin Endocrinol Metab. 2011 Jan. 96(1):E181-8. [Medline].
Hamdy O. The role of adipose tissue as an endocrine gland. Curr Diab Rep. 2005 Oct. 5(5):317-9. [Medline].
Bays H, Blonde L, Rosenson R. Adiposopathy: how do diet, exercise and weight loss drug therapies improve metabolic disease in overweight patients?. Expert Rev Cardiovasc Ther. 2006 Nov. 4(6):871-95. [Medline].
Ketterer C, Heni M, Thamer C, Herzberg-Schäfer SA, Häring HU, Fritsche A. Acute, short-term hyperinsulinemia increases olfactory threshold in healthy subjects. Int J Obes (Lond). 2011 Aug. 35(8):1135-8. [Medline].
Lieb W, Sullivan LM, Harris TB, Roubenoff R, Benjamin EJ, Levy D, et al. Plasma leptin levels and incidence of heart failure, cardiovascular disease, and total mortality in elderly individuals. Diabetes Care. 2009 Apr. 32(4):612-6. [Medline]. [Full Text].
Birketvedt GS, Florholmen J, Sundsfjord J, Osterud B, Dinges D, Bilker W, et al. Behavioral and neuroendocrine characteristics of the night-eating syndrome. JAMA. 1999 Aug 18. 282(7):657-63. [Medline].
Murray PG, Read A, Banerjee I, Whatmore AJ, Pritchard LE, Davies RA, et al. Reduced appetite and body mass index with delayed puberty in a mother and son: association with a rare novel sequence variant in the leptin gene. Eur J Endocrinol. 2011 Apr. 164(4):521-7. [Medline].
Physical Activity: Facts about Physical Activity. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/physicalactivity/data/facts.html. Accessed: January 9, 2013.
Maripuu M, Wikgren M, Karling P, Adolfsson R, Norrback KF. Relative hypocortisolism is associated with obesity and the metabolic syndrome in recurrent affective disorders. J Affect Disord. 2016 Jun 21. 204:187-196. [Medline].
Bouchard C, Tremblay A, Després JP, Nadeau A, Lupien PJ, Thériault G, et al. The response to long-term overfeeding in identical twins. N Engl J Med. 1990 May 24. 322(21):1477-82. [Medline].
Freeman E, Fletcher R, Collins CE, et al. Preventing and treating childhood obesity: time to target fathers. Int J Obes (Lond). 2012 Jan. 36(1):12-5. [Medline].
Chambers JC, Elliott P, Zabaneh D, Zhang W, Li Y, Froguel P, et al. Common genetic variation near MC4R is associated with waist circumference and insulin resistance. Nat Genet. 2008 Jun. 40(6):716-8. [Medline].
Frayling TM, Ong K. Piecing together the FTO jigsaw. Genome Biol. 2011. 12(2):104. [Medline]. [Full Text].
Loos RJ, Lindgren CM, Li S, Wheeler E, Zhao JH, Prokopenko I, et al. Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat Genet. 2008 Jun. 40(6):768-75. [Medline]. [Full Text].
Scuteri A, Sanna S, Chen WM, Uda M, Albai G, Strait J, et al. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet. 2007 Jul. 3(7):e115. [Medline]. [Full Text].
Day FR, Loos RJ. Developments in obesity genetics in the era of genome-wide association studies. J Nutrigenet Nutrigenomics. 2011. 4(4):222-38. [Medline].
Reinehr T, Kleber M, de Sousa G, et al. Leptin concentrations are a predictor of overweight reduction in a lifestyle intervention. Int J Pediatr Obes. May 13 2009;1-9:[Medline].
Cummings DE, Schwartz MW. Melanocortins and body weight: a tale of two receptors. Nat Genet. 2000 Sep. 26(1):8-9. [Medline].
Vaisse C, Clement K, Durand E, Hercberg S, Guy-Grand B, Froguel P. Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity. J Clin Invest. 2000 Jul. 106(2):253-62. [Medline]. [Full Text].
Wardlaw SL. Clinical review 127: Obesity as a neuroendocrine disease: lessons to be learned from proopiomelanocortin and melanocortin receptor mutations in mice and men. J Clin Endocrinol Metab. 2001 Apr. 86(4):1442-6. [Medline].
Gibson WT, Farooqi IS, Moreau M, DePaoli AM, Lawrence E, O'Rahilly S, et al. Congenital leptin deficiency due to homozygosity for the Delta133G mutation: report of another case and evaluation of response to four years of leptin therapy. J Clin Endocrinol Metab. 2004 Oct. 89(10):4821-6. [Medline].
Abbasi A, Corpeleijn E, Postmus D, Gansevoort RT, de Jong PE, Gans RO, et al. Plasma procalcitonin is associated with obesity, insulin resistance, and the metabolic syndrome. J Clin Endocrinol Metab. 2010 Sep. 95(9):E26-31. [Medline].
Yaemsiri S, Slining MM, Agarwal SK. Perceived weight status, overweight diagnosis, and weight control among US adults: the NHANES 2003-2008 Study. Int J Obes (Lond). 2011 Aug. 35(8):1063-70. [Medline].
Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of obesity and trends in body mass index among US children and adolescents, 1999-2010. JAMA. 2012 Feb 1. 307(5):483-90. [Medline].
Laidman J. Obesity's Toll: 1 in 5 Deaths Linked to Excess Weight. Medscape Medical News. Available at http://www.medscape.com/viewarticle/809516. Accessed: August 21, 2013.
Masters RK, Reither EN, Powers DA, Yang YC, Burger AE, Link BG. The Impact of Obesity on US Mortality Levels: The Importance of Age and Cohort Factors in Population Estimates. Am J Public Health. 2013 Aug 15.
Ludwig J, Sanbonmatsu L, Gennetian L, et al. Neighborhoods, obesity, and diabetes--a randomized social experiment. N Engl J Med. 2011 Oct 20. 365(16):1509-19. [Medline].
Molarius A, Seidell JC, Sans S, Tuomilehto J, Kuulasmaa K. Varying sensitivity of waist action levels to identify subjects with overweight or obesity in 19 populations of the WHO MONICA Project. J Clin Epidemiol. 1999 Dec. 52(12):1213-24. [Medline].
Molarius A, Seidell JC, Sans S, Tuomilehto J, Kuulasmaa K. Waist and hip circumferences, and waist-hip ratio in 19 populations of the WHO MONICA Project. Int J Obes Relat Metab Disord. 1999 Feb. 23(2):116-25. [Medline].
Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ, et al. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9·1 million participants. Lancet. 2011 Feb 12. 377(9765):557-67. [Medline].
Neel JV. The "thrifty genotype" in 1998. Nutr Rev. 1999 May. 57(5 Pt 2):S2-9. [Medline].
Metcalf BS, Hosking J, Frémeaux AE, Jeffery AN, Voss LD, Wilkin TJ. BMI was right all along: taller children really are fatter (implications of making childhood BMI independent of height) EarlyBird 48. Int J Obes (Lond). 2011 Apr. 35(4):541-7. [Medline].
The NS, Suchindran C, North KE, Popkin BM, Gordon-Larsen P. Association of adolescent obesity with risk of severe obesity in adulthood. JAMA. 2010 Nov 10. 304(18):2042-7. [Medline]. [Full Text].
Allison DB, Fontaine KR, Manson JE, Stevens J, VanItallie TB. Annual deaths attributable to obesity in the United States. JAMA. 1999 Oct 27. 282(16):1530-8. [Medline].
[Guideline] Expert Panel on the Identification, Evaluation, and Treatment of Overweight Adults. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: executive summary. Expert Panel on the Identification, Evaluation, and Treatment of Overweight in Adults. Am J Clin Nutr. 1998 Oct. 68(4):899-917. [Medline].
Bray GA. Health hazards of obesity. Endocrinol Metab Clin North Am. 1996 Dec. 25(4):907-19. [Medline].
Flegal KM, Graubard BI, Williamson DF, Gail MH. Excess deaths associated with underweight, overweight, and obesity. JAMA. 2005 Apr 20. 293(15):1861-7. [Medline].
Zheng W, McLerran DF, Rolland B, Zhang X, Inoue M, Matsuo K, et al. Association between body-mass index and risk of death in more than 1 million Asians. N Engl J Med. 2011 Feb 24. 364(8):719-29. [Medline].
Berrington de Gonzalez A, Hartge P, Cerhan JR, Flint AJ, Hannan L, MacInnis RJ, et al. Body-mass index and mortality among 1.46 million white adults. N Engl J Med. 2010 Dec 2. 363(23):2211-9. [Medline]. [Full Text].
Boggs DA, Rosenberg L, Cozier YC, Wise LA, Coogan PF, Ruiz-Narvaez EA, et al. General and abdominal obesity and risk of death among black women. N Engl J Med. 2011 Sep 8. 365(10):901-8. [Medline].
Stessman J, Jacobs JM, Ein-Mor E, Bursztyn M. Normal body mass index rather than obesity predicts greater mortality in elderly people: the Jerusalem longitudinal study. J Am Geriatr Soc. 2009 Dec. 57(12):2232-8. [Medline].
Tamakoshi A, Yatsuya H, Lin Y, Tamakoshi K, Kondo T, Suzuki S, et al. BMI and all-cause mortality among Japanese older adults: findings from the Japan collaborative cohort study. Obesity (Silver Spring). 2010 Feb. 18(2):362-9. [Medline].
Wadden TA, Neiberg RH, Wing RR, Clark JM, Delahanty LM, Hill JO, et al. Four-year weight losses in the Look AHEAD study: factors associated with long-term success. Obesity (Silver Spring). 2011 Oct. 19(10):1987-98. [Medline]. [Full Text].
Elbel B, Gyamfi J, Kersh R. Child and adolescent fast-food choice and the influence of calorie labeling: a natural experiment. Int J Obes (Lond). 2011 Apr. 35(4):493-500. [Medline].
Waters E, de Silva-Sanigorski A, Hall BJ, et al. Interventions for preventing obesity in children. Cochrane Database Syst Rev. 2011 Dec 7. 12:CD001871. [Medline].
American Association of Clinical Endocrinologists Statement on the Use of A1C for the Diagnosis of Diabetes. Available at http://emedicine.medscape.com/article/117853-workup. Accessed: August 6 2012.
[Guideline] Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010 Jan. 33 Suppl 1:S62-9. [Medline]. [Full Text].
[Guideline] Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. J Am Coll Cardiol. 2013. [Medline]. [Full Text].
Nainggolan L. New obesity guidelines: authoritative 'roadmap' to treatment. Medscape Medical News. November 12, 2013. [Full Text].
Tucker ME. New US obesity guidelines. Treat the weight first. Medscape Medical News. Available at http://www.medscape.com/viewarticle/838285.
Apovian CM, Aronne LJ, Bessesen DH, et al. Pharmacological management of obesity: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2015 Feb. 100(2):342-62. [Medline].
Jolly K, Lewis A, Beach J, et al. Comparison of range of commercial or primary care led weight reduction programmes with minimal intervention control for weight loss in obesity: Lighten Up randomised controlled trial. BMJ. 2011 Nov 3. 343:d6500. [Medline]. [Full Text].
Bray GA. Medications for weight reduction. Med Clin North Am. 2011 Sep. 95(5):989-1008. [Medline].
Wing RR, Lang W, Wadden TA, Safford M, Knowler WC, Bertoni AG, et al. Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes. Diabetes Care. 2011 Jul. 34(7):1481-6. [Medline]. [Full Text].
Stolley MR, Fitzgibbon ML, Schiffer L, Sharp LK, Singh V, Van Horn L, et al. Obesity reduction black intervention trial (ORBIT): six-month results. Obesity (Silver Spring). 2009 Jan. 17(1):100-6. [Medline].
Blüher M, Rudich A, Kloting N, et al. Two patterns of adipokine and other biomarker dynamics in a long-term weight loss intervention. Diabetes Care. 2012 Feb. 35(2):342-9. [Medline]. [Full Text].
Sumithran P, Prendergast LA, Delbridge E, et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med. 2011 Oct 27. 365(17):1597-604. [Medline].
Maffeis C. Childhood obesity: the genetic-environmental interface. Baillieres Best Pract Res Clin Endocrinol Metab. 1999 Apr. 13(1):31-46. [Medline].
Proimos J, Sawyer S. Obesity in childhood and adolescence. Aust Fam Physician. 2000 Apr. 29(4):321-7. [Medline].
Harsha DW, Bray GA. Body composition and childhood obesity. Endocrinol Metab Clin North Am. 1996 Dec. 25(4):871-85. [Medline].
Older Adults and the Elderly. In: Human Energy Requirements: Report of a Joint FAO/WHO/UNU Expert Consultation. Rome, 17-24 October 2001. Food and Agriculture Organization of the UN. Available at http://www.fao.org/docrep/007/y5686e/y5686e09.htm#bm9.
Brooks M. Standard '1-MET' Value Invalid in Overweight/Obese. Medscape Medical News. Available at http://www.medscape.com/viewarticle/821375. Accessed: March 10, 2014.
Wilms B, Ernst B, Thurnheer M, Weisser B, Schultes B. Correction factors for the calculation of metabolic equivalents (MET) in overweight to extremely obese subjects. Int J Obes (Lond). 2014 Feb 7. [Medline].
Foster GD, Wyatt HR, Hill JO, Makris AP, Rosenbaum DL, Brill C, et al. Weight and metabolic outcomes after 2 years on a low-carbohydrate versus low-fat diet: a randomized trial. Ann Intern Med. 2010 Aug 3. 153(3):147-57. [Medline]. [Full Text].
Shai I, Schwarzfuchs D, Henkin Y, Shahar DR, Witkow S, Greenberg I, et al. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med. 2008 Jul 17. 359(3):229-41.
Larsen TM, Dalskov SM, van Baak M, Jebb SA, Papadaki A, Pfeiffer AF, et al. Diets with high or low protein content and glycemic index for weight-loss maintenance. N Engl J Med. 2010 Nov 25. 363(22):2102-13. [Medline].
Dansinger ML, Gleason JA, Griffith JL, Selker HP, Schaefer EJ. Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial. JAMA. 2005 Jan 5. 293(1):43-53. [Medline].
Very low calorie diets. Drug Ther Bull. 2012 May. 50(5):54-7. [Medline].
Van Nieuwenhove Y, Dambrauskas Z, Campillo-Soto A, van Dielen F, Wiezer R, Janssen I, et al. Preoperative very low-calorie diet and operative outcome after laparoscopic gastric bypass: a randomized multicenter study. Arch Surg. 2011 Nov. 146(11):1300-5. [Medline].
Dennis EA, Dengo AL, Comber DL, Flack KD, Savla J, Davy KP, et al. Water consumption increases weight loss during a hypocaloric diet intervention in middle-aged and older adults. Obesity (Silver Spring). 2010 Feb. 18(2):300-7. [Medline]. [Full Text].
Dubnov-Raz G, Constantini NW, Yariv H, Nice S, Shapira N. Influence of water drinking on resting energy expenditure in overweight children. Int J Obes (Lond). 2011 Oct. 35(10):1295-300. [Medline].
Wiesner S, Haufe S, Engeli S, Mutschler H, Haas U, Luft FC, et al. Influences of normobaric hypoxia training on physical fitness and metabolic risk markers in overweight to obese subjects. Obesity (Silver Spring). 2010 Jan. 18(1):116-20. [Medline].
Jakicic JM, Marcus BH, Lang W, Janney C. Effect of exercise on 24-month weight loss maintenance in overweight women. Arch Intern Med. 2008 Jul 28. 168(14):1550-9; discussion 1559-60. [Medline]. [Full Text].
Ballor DL, Poehlman ET. Exercise-training enhances fat-free mass preservation during diet-induced weight loss: a meta-analytical finding. Int J Obes Relat Metab Disord. 1994 Jan. 18(1):35-40. [Medline].
Villareal DT, Chode S, Parimi N, Sinacore DR, Hilton T, Armamento-Villareal R, et al. Weight loss, exercise, or both and physical function in obese older adults. N Engl J Med. 2011 Mar 31. 364(13):1218-29. [Medline]. [Full Text].
Goodpaster BH, Delany JP, Otto AD, Kuller L, Vockley J, South-Paul JE, et al. Effects of diet and physical activity interventions on weight loss and cardiometabolic risk factors in severely obese adults: a randomized trial. JAMA. 2010 Oct 27. 304(16):1795-802. [Medline]. [Full Text].
Hankinson AL, Daviglus ML, Bouchard C, Carnethon M, Lewis CE, Schreiner PJ, et al. Maintaining a high physical activity level over 20 years and weight gain. JAMA. 2010 Dec 15. 304(23):2603-10. [Medline].
Rejeski WJ, Brubaker PH, Goff DC Jr, Bearon LB, McClelland JW, Perri MG, et al. Translating weight loss and physical activity programs into the community to preserve mobility in older, obese adults in poor cardiovascular health. Arch Intern Med. 2011 May 23. 171(10):880-6. [Medline].
Van Dorsten B, Lindley EM. Cognitive and behavioral approaches in the treatment of obesity. Med Clin North Am. 2011 Sep. 95(5):971-88. [Medline].
Morgan PJ, Lubans DR, Callister R, Okely AD, Burrows TL, Fletcher R, et al. The 'Healthy Dads, Healthy Kids' randomized controlled trial: efficacy of a healthy lifestyle program for overweight fathers and their children. Int J Obes (Lond). 2011 Mar. 35(3):436-47. [Medline].
Mozaffarian D, Hao T, Rimm EB, Willett WC, Hu FB. Changes in diet and lifestyle and long-term weight gain in women and men. N Engl J Med. 2011 Jun 23. 364(25):2392-404. [Medline]. [Full Text].
Nedeltcheva AV, Kilkus JM, Imperial J, Schoeller DA, Penev PD. Insufficient sleep undermines dietary efforts to reduce adiposity. Ann Intern Med. 2010 Oct 5. 153(7):435-41. [Medline]. [Full Text].
FDA Expands Warning to Consumers About Tainted Weight Loss Pills. US Food and Drug Administration. January 8, 2009. Available at http://www.fda.gov/newsevents/newsroom/pressannouncements/2008/ucm116998.htm. Accessed: January, 2013.
United States Food and Drug Administration. BMPEA in Dietary Supplements. Available at http://www.fda.gov/Food/DietarySupplements/QADietarySupplements/ucm443790.htm. Accessed: 2015 April 27.
Heck AM, Yanovski JA, Calis KA. Orlistat, a new lipase inhibitor for the management of obesity. Pharmacotherapy. 2000 Mar. 20(3):270-9. [Medline].
US Food and Drug Administration. FDA approves Belviq to treat some overweight or obese adults. June 27, 2012. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm309993.htm. Accessed: July 12, 2012.
Schedules of Controlled Substances: Placement of Lorcaserin Into Schedule IV. Drug Enforcement Administration. Available at http://www.deadiversion.usdoj.gov/fed_regs/rules/2012/fr1219.htm. Accessed: December 28, 2012.
Smith SR, Weissman NJ, Anderson CM, Sanchez M, Chuang E, Stubbe S, et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med. 2010 Jul 15. 363(3):245-56. [Medline]. [Full Text].
Fidler MC, Sanchez M, Raether B, Weissman NJ, Smith SR, Shanahan WR, et al. A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. J Clin Endocrinol Metab. 2011 Oct. 96(10):3067-77. [Medline].
O'Neil PM, Smith SR, Weissman NJ, Fidler MC, Sanchez M, Zhang J, et al. Randomized placebo-controlled clinical trial of lorcaserin for weight loss in type 2 diabetes mellitus: the BLOOM-DM study. Obesity (Silver Spring). 2012 Jul. 20(7):1426-36. [Medline].
FDA News Release. FDA approves weight-management drug Saxenda. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427913.htm. Accessed: December 23, 2014.
Serretti A, Mandelli L. Antidepressants and body weight: a comprehensive review and meta-analysis. J Clin Psychiatry. 2010 Oct. 71(10):1259-72. [Medline].
Goldfield GS, Lorello C, Doucet E. Methylphenidate reduces energy intake and dietary fat intake in adults: a mechanism of reduced reinforcing value of food?. Am J Clin Nutr. 2007 Aug. 86(2):308-15. [Medline].
Gadde KM, Franciscy DM, Wagner HR 2nd, Krishnan KR. Zonisamide for weight loss in obese adults: a randomized controlled trial. JAMA. 2003 Apr 9. 289(14):1820-5. [Medline].
Lustig RH, Hinds PS, Ringwald-Smith K, Christensen RK, Kaste SC, Schreiber RE, et al. Octreotide therapy of pediatric hypothalamic obesity: a double-blind, placebo-controlled trial. J Clin Endocrinol Metab. 2003 Jun. 88(6):2586-92. [Medline].
Desilets AR, Dhakal-Karki S, Dunican KC. Role of metformin for weight management in patients without type 2 diabetes. Ann Pharmacother. 2008 Jun. 42(6):817-26. [Medline].
Vilsbøll T, Christensen M, Junker AE, Knop FK, Gluud LL. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ. 2012 Jan 10. 344:d7771. [Medline]. [Full Text].
Gadde KM, Xiong GL. Bupropion for weight reduction. Expert Rev Neurother. 2007 Jan. 7(1):17-24. [Medline].
Black SC. Cannabinoid receptor antagonists and obesity. Curr Opin Investig Drugs. 2004 Apr. 5(4):389-94. [Medline].
Van Gaal LF, Rissanen AM, Scheen AJ, et al. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet. Apr 16-22 2005. 365(9468):1389-97.
Cox SL. Rimonabant hydrochloride: an investigational agent for the management of cardiovascular risk factors. Drugs Today (Barc). 2005 Aug. 41(8):499-508. [Medline].
Fernandez JR, Allison DB. Rimonabant Sanofi-Synthélabo. Curr Opin Investig Drugs. 2004 Apr. 5(4):430-5. [Medline].
Nagao T, Meguro S, Hase T, Otsuka K, Komikado M, Tokimitsu I, et al. A catechin-rich beverage improves obesity and blood glucose control in patients with type 2 diabetes. Obesity (Silver Spring). 2009 Feb. 17(2):310-7. [Medline].
Dunican KC, Adams NM, Desilets AR. The role of pramlintide for weight loss. Ann Pharmacother. 2010 Mar. 44(3):538-45. [Medline].
Batterham RL, Cohen MA, Ellis SM, Le Roux CW, Withers DJ, Frost GS, et al. Inhibition of food intake in obese subjects by peptide YY3-36. N Engl J Med. 2003 Sep 4. 349(10):941-8. [Medline].
Boggiano MM, Chandler PC, Oswald KD, Rodgers RJ, Blundell JE, Ishii Y. PYY3-36 as an anti-obesity drug target. Obes Rev. 2005 Nov. 6(4):307-22. [Medline].
Roth CL, Enriori PJ, Harz K, Woelfle J, Cowley MA, Reinehr T. Peptide YY is a regulator of energy homeostasis in obese children before and after weight loss. J Clin Endocrinol Metab. 2005 Dec. 90(12):6386-91. [Medline].
Moon HS, Matarese G, Brennan AM, Chamberland JP, Liu X, Fiorenza CG, et al. Efficacy of metreleptin in obese patients with type 2 diabetes: cellular and molecular pathways underlying leptin tolerance. Diabetes. 2011 Jun. 60(6):1647-56. [Medline]. [Full Text].
Ravussin E, Smith SR, Mitchell JA, Shringarpure R, Shan K, Maier H, et al. Enhanced weight loss with pramlintide/metreleptin: an integrated neurohormonal approach to obesity pharmacotherapy. Obesity (Silver Spring). 2009 Sep. 17(9):1736-43. [Medline]. [Full Text].
Tam CS, Lecoultre V, Ravussin E. Novel strategy for the use of leptin for obesity therapy. Expert Opin Biol Ther. 2011 Dec. 11(12):1677-85. [Medline].
Sjöström L, Peltonen M, Jacobson P, Sjöström CD, Karason K, Wedel H, et al. Bariatric surgery and long-term cardiovascular events. JAMA. 2012 Jan 4. 307(1):56-65. [Medline].
Flum DR, Belle SH, King WC, Wahed AS, Berk P, Chapman W, et al. Perioperative safety in the longitudinal assessment of bariatric surgery. N Engl J Med. 2009 Jul 30. 361(5):445-54. [Medline]. [Full Text].
Maggard MA, Shugarman LR, Suttorp M, Maglione M, Sugerman HJ, Livingston EH, et al. Meta-analysis: surgical treatment of obesity. Ann Intern Med. 2005 Apr 5. 142(7):547-59. [Medline].
Tucker ME. New Bariatric Surgery Guidelines Reflect Rapidly Evolving Field. Medscape Medical News. Mar 28 2013. Available at http://www.medscape.com/viewarticle/781619. Accessed: Apr 3 2013.
Fiore K. New Guidelines for Weight-Loss Surgery Upgrade Sleeve Procedure. MedPage Today. Available at http://www.medpagetoday.com/Endocrinology/Obesity/38112?utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=WC&xid=NL_DHE_2013firstname.lastname@example.org&mu_id=5780408. Accessed: Apr 3 2013.
Mechanick JI, Youdim A, Jones DB, Garvey WT, Hurley DL, McMahon MM, et al. Clinical Practice Guidelines for the Perioperative Nutritional, Metabolic, and Nonsurgical Support of the Bariatric Surgery Patient - 2013 Update: Cosponsored by American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery. Endocr Pract. 2013 Mar 25. e1-e36. [Medline].
Ashley S, Bird DL, Sugden G, Royston CM. Vertical banded gastroplasty for the treatment of morbid obesity. Br J Surg. 1993 Nov. 80(11):1421-3. [Medline].
Flickinger EG, Pories WJ, Meelheim HD, Sinar DR, Blose IL, Thomas FT. The Greenville gastric bypass. Progress report at 3 years. Ann Surg. 1984 May. 199(5):555-62. [Medline]. [Full Text].
Plecka Östlund M, Marsk R, Rasmussen F, Lagergren J, Näslund E. Morbidity and mortality before and after bariatric surgery for morbid obesity compared with the general population. Br J Surg. 2011 Jun. 98(6):811-6. [Medline].
Mingrone G, Panunzi S, De Gaetano A, Guidone C, Iaconelli A, Leccesi L, et al. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med. 2012 Apr 26. 366(17):1577-85. [Medline]. [Full Text].
Søvik TT, Aasheim ET, Taha O, Engström M, Fagerland MW, Björkman S, et al. Weight loss, cardiovascular risk factors, and quality of life after gastric bypass and duodenal switch: a randomized trial. Ann Intern Med. 2011 Sep 6. 155(5):281-91. [Medline].
Hedberg J, Sundbom M. Superior weight loss and lower HbA1c 3 years after duodenal switch compared with Roux-en-Y gastric bypass--a randomized controlled trial. Surg Obes Relat Dis. 2012 May-Jun. 8(3):338-43. [Medline].
Cigaina V. Gastric pacing as therapy for morbid obesity: preliminary results. Obes Surg. 2002 Apr. 12 Suppl 1:12S-16S. [Medline].
Klein S, Fontana L, Young VL, et al. Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease. N Engl J Med. Jun 17 2004. 350(25):2549-57.
Koch TR, Finelli FC. Postoperative metabolic and nutritional complications of bariatric surgery. Gastroenterol Clin North Am. 2010 Mar. 39(1):109-24. [Medline].
Abbott Laboratories agrees to withdraw its obesity drug Meridia. FDA, U.S. Food and Drug Administration. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm228812.htm. Accessed: October 8, 2010.
Anderson JW, Jhaveri MA. Reductions in medications with substantial weight loss with behavioral intervention. Curr Clin Pharmacol. 2010 Nov. 5(4):232-8. [Medline].
Food and Drug Administration. FDA approves weight-management drug Qsymia. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm312468.htm. Accessed: August 7, 2012.
Grudell AB, Sweetser S, Camilleri M, Eckert DJ, Vazquez-Roque MI, Carlson PJ, et al. A controlled pharmacogenetic trial of sibutramine on weight loss and body composition in obese or overweight adults. Gastroenterology. 2008 Oct. 135(4):1142-54. [Medline]. [Full Text].
James WP, Caterson ID, Coutinho W, Finer N, Van Gaal LF, Maggioni AP, et al. Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N Engl J Med. 2010 Sep 2. 363(10):905-17. [Medline].
Laidman J. Obesity Thresholds Accurately Predict Adolescent Health Risk. Medscape Medical News. Jan 29 2014. [Full Text].
Laurson KR, Welk GJ, Eisenmann JC. Diagnostic performance of BMI percentiles to identify adolescents with metabolic syndrome. Pediatrics. 2014 Feb. 133(2):e330-8. [Medline].
Makowski CT, Gwinn KM, Hurren KM. Naltrexone/bupropion: an investigational combination for weight loss and maintenance. Obes Facts. 2011. 4(6):489-94. [Medline].
Nainggolan L. Gastric band is first step surgery for morbidly obese teens. Medscape Medical News. May 29, 2014. [Full Text].
Nainggolan L. FDA Approves Bupropion/Naltrexone (Contrave) for Obesity. Medscape Medical News. Available at http://www.staging.medscape.com/viewarticle/831513. Accessed: September 14, 2014.
Schauer PR, Kashyap SR, Wolski K, Brethauer SA, Kirwan JP, Pothier CE, et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med. 2012 Apr 26. 366(17):1567-76. [Medline]. [Full Text].
Sjöström L, Narbro K, Sjöström CD, Karason K, Larsson B, Wedel H, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007 Aug 23. 357(8):741-52. [Medline].