Current Drug Therapy

Pharmacotherapy for obesity: What you need to know

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Weight-loss drugs are being evaluated for their role in obesity management. This article reviews the available weight-loss drugs, their efficacy and side effects, and their best clinical use.


  • Weight-loss drugs should only be used in combination with lifestyle modification.
  • Preparations that combine 2 drugs have greater weight-loss benefits and better side-effect profiles.
  • Weight-loss drugs should be discontinued if substantial (5%) weight loss has not occurred by 12 weeks.
  • All weight-loss drugs are contraindicated in pregnancy.



Weight-loss drugs are not magic pills, but they can help patients lose about 10 to 25 more pounds than they otherwise could, when used in a program that includes diet, exercise, and other lifestyle changes.

Drugs approved by the US Food and Drug Administration for treating obesity
This article reviews current drug therapy for obesity, including dosages, approved duration of use, mechanisms of action, adverse effects, potential interactions, contraindications, and data on efficacy. Table 1 summarizes the drugs currently approved by the US Food and Drug Administration (FDA) for this indication.

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Obesity is a major public health challenge in the United States, with nearly 37% of adults classified as obese.1 The prevalence has increased more than 75% since 1980,2 and it is estimated that 51% of US adults will be obese by 2030.3 Obesity is the second-leading cause of preventable deaths, after smoking.4

Obesity increases the risk of many chronic medical conditions, including type 2 diabetes mellitus, heart disease, hypertension, stroke, nonalcoholic fatty liver disease, osteoarthritis, and cancers of the breast, colon, endometrium, and kidney.5


Guidelines from the major obesity societies recommend that all weight-loss programs have a lifestyle component that includes a low-calorie diet, increased physical activity, and behavioral therapy, to which pharmacotherapy may be added as an adjunct.6–8

Weight-loss medications are indicated for patients who have a body mass index (BMI) of at least 30 kg/m2 or who have obesity-associated comorbidities and a BMI of at least 27 kg/m2. However, the best results are achieved when pharmacotherapy is combined with lifestyle modification.9

Treatments by body mass index and comorbidity
Weight-loss surgery is a safe and effective option for patients with a BMI of at least 40 kg/m2 or, with comorbidities, a BMI of at least 35 kg/m2 (Table 2). About 15 million Americans have a BMI of at least 40 kg/m2. Although bariatric surgery is the most efficient and longest-lasting treatment, only 1% of the eligible population receives surgical treatment.10


The earliest drugs to induce weight loss, which worked mainly by increasing metabolism, included thyroid hormone, amphetamines (which also suppress appetite), and dinitrophenol (a pesticide). Adverse reactions limited their usefulness: cardiovascular effects with thyroid hormones, abuse potential with amphetamines, and neuropathy and cataracts with dinitrophenol.

Researchers then looked to drugs that could suppress appetite like amphetamines do, but without the potential for abuse. Medications that increased levels of norepinephrine and serotonin, both by increasing release and decreasing reuptake of these neuromodulators, had some success. But again, serious adverse effects occurred, and several drugs had to be withdrawn from the market.

The most publicized of these withdrawals was for the combination fenfluramine and phentermine (“fen-phen”) and its cousin dexfenfluramine (Redux). Up to 30% of patients taking fenfluramine-phentermine developed echocardiographic evidence of valvular heart disease.11 Fenfluramine also increased the risk of pulmonary hypertension. These findings led to the 1997 withdrawal of these drugs from the US market.

Sibutramine (Meridia), a norepinephrine and serotonin reuptake inhibitor, was approved for weight loss in 1997. Increases in blood pressure and heart rate were noted in the initial trial,12 and then a postmarketing study found increased rates of nonfatal myocardial infarction and stroke in patients with preexisting cardiovascular disease or diabetes mellitus.13 Based on these results, sibutramine was withdrawn from both US and European markets.

Rimonabant (Acomplia, Zimulti), a cannabinoid-receptor inhibitor, was approved in Europe in 2006, but its approval was withdrawn just 2 years later because of increased suicidality in a postmarketing study.14 It was never approved for use in the United States.


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