Pharmacological Management of Obesity: Agents and Mechanisms of Action

Summary of the Endocrine Society's Guideline on the Pharmacological Management of Obesity

This article is the third in a 4-part series on the Endocrine Society’s clinical practice guideline on the pharmacological management of obesity. This section presents agents approved by the U.S. Food and Drug Administration (FDA) for the treatment of obesity and their mechanisms of action.

Nine pharmacotherapies for obesity were approved in the United States at the time of the guideline’s publication in December 2014, and the guideline addressed seven of them (see Table).  Benzphetamine and phendimetrazine were not included in the review.  Except for orlistat, these agents all work primarily by promoting satiety through stimulation of pro-opiomelanocortin (POMC) neurons in the arcuate nucleus. Orlistat works by blocking absorption of 25% to 30% of fat calories.

Recommendation on Use of Pharmacotherapy for Chronic Weight Management
The task force recommends use of FDA-approved weight loss medications to improve obesity-related comborbidities and adherence to behavior changes in people with a body mass index (BMI) ≥30 kg/m2 or a BMI ≥27 kg/m2 and at least 1 obesity-related comorbidity (eg, hypertension, dyslipidemia, type 2 diabetes, and obstructive sleep apnea). These medications should be used as adjuncts to healthy eating, good nutrition, increased physical activity, and behavior modifications.

The dose of each agent should be escalated based on efficacy and tolerability and should not exceed the maximum dose listed on the agent’s prescribing information. The efficacy and safety of weight loss medications should be assessed monthly for the first 3 months and every 3 months thereafter. Treatment efficacy is defined as weight loss of ≥5% at 3 months.

Can Phentermine Be Used for Chronic Weight Management?
Phentermine is approved for short-term use only (ie, 3 months). While there is a lack of published controlled studies on the safety and efficacy of long-term phentermine use, the Task Force notes that long-term use may be reasonable for patients with no evidence of serious cardiovascular disease or a history of psychiatric disease or substance abuse, who do not experience a clinically significant increase in pulse or blood pressure when taking the medication, and who lose a significant amount of weight while using phentermine.

Avoid Off-Label Use of Medications for Weight Loss
The task force does not recommend use of any medications off-label exclusively for weight loss. Physicians or researchers with expertise in weight management may attempt to use such agents (eg, bupropion, exenatide, liraglutide, metformin, methylphenidate, thyroid hormones, topiramate, and zonisamide) in well-informed patients.

When treating comorbid conditions in patients with obesity, avoid agents with a potential for weight gain. Therapeutic alternatives to these agents are described in Part 4 of this series.

June 6, 2015

Read other sections of the clinical practice guideline summary:

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Alternatives to Medications That Cause Weight Gain
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