The injectable glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide (Wegovy), which was approved by the FDA in 2021 for chronic weight management in adults, has now been approved for chronic weight management in children ≥12 years old with an initial BMI in the ≥95th percentile for age and sex.Semaglutide is also available as Ozempic and Rybelsus for treatment of type 2 diabetes in adults.

Adults with a body mass index (BMI) between 25 and 29.9 kg/m² are considered overweight. Those with a BMI ≥30 are considered obese. The initial recommendation for any weight loss effort is to achieve a 5-10% reduction in weight, which has been associated with a reduction in the risk of developing type 2 diabetes, hypertension, and dyslipidemia. Diet, exercise, and behavior modification are the preferred methods for losing weight, but long-term weight maintenance can be difficult. Several drugs and devices are FDA-approved for weight reduction and maintenance of weight loss.

View the Comparison Table: Some FDA-Approved Drugs for Weight Management

Plenity (Gelesis), a nonsystemic oral superabsorbent hydrogel formulation of cellulose and citric acid is now available. It was cleared by the FDA in 2019 to aid in weight management together with diet and exercise in overweight and obese adults (BMI of 25-40 kg/m2). It is classified by the FDA as a device because the contents of the capsule are not absorbed systemically. Plenity is the first ingested, transient, space-occupying hydrogel to be marketed in the US and the only weight management treatment available by prescription for patients with a BMI of 25-30 kg/m², regardless of comorbidities. Low-dose orlistat (Alli) has been available over the counter for patients with a BMI ≥25 kg/m² for years.

Adults with a body mass index (BMI) between 25 and 29.9 kg/m2 are considered overweight. Those with a BMI ≥30 are considered obese. The initial recommendation for any weight loss effort is to achieve a 5-10% reduction in weight, which has been associated with a reduction in the risk of developing type 2 diabetes, hypertension, and dyslipidemia. Diet, exercise, and behavior modification are the preferred methods for losing weight, but long-term weight maintenance can be difficult. Several drugs are FDA-approved for weight reduction and maintenance (see Table 1), and procedures such as endoscopic placement of dilated balloons have produced beneficial short-term results (see Table 2), but bariatric surgery has been the most effective intervention for sustainable long-term weight loss and reduction of obesity-related comorbidities.

View the Comparison Table: Some FDA-Approved Drugs for Weight Management

The injectable glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide, previously approved by the FDA for treatment of type 2 diabetes as Victoza, has now also been approved at a higher dose as Saxenda (Novo Nordisk) for chronic weight management in adults with a BMI ≥30, or a BMI ≥27 with a weight-related comorbidity such as hypertension, dyslipidemia, or diabetes.

Adults with a body mass index (BMI) between 25 and 29.9 kg/m² are considered overweight. Those with a BMI ≥30 are considered obese. Losing even a small amount of weight and increasing physical activity can prevent some of the complications of obesity, particularly type 2 diabetes. Diet and exercise are the preferred methods for losing weight, but long-term failure rates are high. Several drugs have been approved by the FDA for weight reduction, but adherence is poor, adverse effects are common, and patients usually regain the lost weight when the drug is stopped. Bariatric surgery can produce substantial weight loss and significantly reduce obesity-related comorbidities; long-term data on its safety are encouraging, but still limited. Guidelines for the management of overweight or obese adults have recently been published.

The FDA has approved a fixed-dose combination of the opioid receptor antagonist naltrexone (ReVia, and others) and the antidepressant and smoking cessation agent bupropion (Wellbutrin SR, Zyban, and others), as Contrave (Orexigen/Takeda) for weight loss. The combination was approved for use as an adjunct to diet and increased physical activity in patients with a body mass index (BMI) ≥30 kg/m² or a BMI ≥27 kg/m² and one or more weight-related comorbidities such as hypertension, diabetes, or dyslipidemia. Naltrexone/bupropion is not a controlled substance.

In 2013 the FDA approved one new drug and a new combination of 2 old drugs as adjuncts to lifestyle changes for chronic weight management. Lorcaserin (lor-ca-SER-in; Belviq – Arena/Esai) is a selective serotonin 2C receptor agonist. Qsymia (Vivus) is a fixed-dose combination of the weight-loss drug phentermine and an extended-release (ER) formulation of topiramate. The new products are approved for use in obese patients (body mass index [BMI] of ≥30 kg/m²) and for patients who are overweight (BMI ≥27 kg/m²) and have one weight-related risk factor such as hypertension, dyslipidemia or type 2 diabetes.

Adults with a body mass index (BMI=kg/m²) of 25-<30 are considered overweight; those with a BMI of ≥30 are considered obese.

Losing even a small amount of weight and increasing physical activity can prevent some of the complications of obesity, particularly type 2 diabetes. Diet and exercise are the preferred methods for losing weight but are associated with high long-term failure rates. Drugs may help some patients, but all currently available drugs for weight reduction have drawbacks. Gastric surgery can produce marked weight loss in the severely obese, but long-term data on safety are limited.

The FDA has approved over-the-counter (OTC) sale of the weight-loss drug orlistat (Xenical – Roche)1 as alli (GlaxoSmithKline), to be used in combination with a reduced-calorie, low-fat diet. Orlistat binds to gastric and pancreatic lipases, preventing absorption of about 30% of dietary fat with the 120-mg prescription dose, and 25% with the 60-mg OTC dose. A 16-week controlled trial of the OTC dose (60 mg 3 times daily with meals) in overweight, not obese, patients (average BMI 26.8) on a reduced-calorie, low-fat diet found that patients taking the drug lost 1.15 kg more than those taking placebo.2

Orlistat causes flatulence with oily spotting, loose stools, fecal urgency and occasional incontinence in 20-40% of patients on a low-fat diet; these effects presumably would be more frequent and more severe with a higher fat intake or self-prescription of higher-thanrecommended doses. The drug also interferes with absorption of fat-soluble vitamins (A, D, E, K); the manufacturer recommends that patients also take a multivitamin supplement at bedtime. Orlistat can increase the anticoagulant effect of warfarin and may interfere with the absorption of other drugs.

A “starter pack” of 90 capsules of alli (60 mg each) costs $62.99, compared to $224.64 for 90 capsules of Xenical (120 mg each).3

1. Orlistat for obesity. Med Lett Drugs Ther 1999; 41:55.

2. JW Anderson et al. Low-dose orlistat effects on body weight of mildly to moderately overweight individuals: a 16 week, double-blind, placebo-controlled trial. Ann Pharmacother 2006; 40:1717.

3. Cost based on information from drugstore.com (June 11, 2007).

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The latest definitions of overweight and obesity are based on body mass index (BMI). The BMI is calculated by dividing the weight in kilograms by the square of the height in meters (kg/m²). More than half of American adults are considered overweight with a BMI of ≥25, and about one third are obese with a BMI of ≥30. All ages seem to be affected; the proportion of children and adolescents who are overweight has more than doubled in the past 25 years. There is no lack of effort to treat obesity: drugs, diets and programs to change lifestyle are the basis for a large and flourishing industry. The frequent failure of diet and drug treatment sometimes leads to recommendations for surgery, usually restricted to those with a BMI ≥40.

Orlistat, a lipase inhibitor that decreases absorption of fat from the gastrointestinal tract, is now available for treatment of obesity.