The FDA's assessment of two drugs for chronic weight management.

n engl j med 367;17 nejm.org october 25, 2012 1577 are manifold, potentially involving all major organ systems and contributing to reduced quality of life. The goal of all obesity therapies is negative energy balance. Drugs have long been used in an attempt to achieve this goal. However, numerous oncepromising weight-loss drugs have been abandoned because of serious toxic effects: aminorex (which caused pulmonary hypertension), fenfluramine and dexfenfluramine (valvulopathy), phenylpropanolamine (stroke), rimonabant (suicidal ideation and behavior), and most recently sibutramine (myocardial infarction and stroke). The removal of sibutramine from the market left orlistat as the only prescription drug approved for the long-term treatment of obesity. It was with this troubled history and the undeniable need for effective, safe weight-loss drugs in mind that we at the Food and Drug Administration (FDA) recently approved two new drugs as adjuncts to a reduced-calorie diet and increased physical activity for chronic weight management in adults who are obese (defined as having a body-mass index [BMI; the weight in kilograms divided by the square of the height in meters] of ≥30) or overweight (BMI ≥27) with at least one weight-related coexisting condition. Belviq (lorcaserin, Arena Pharmaceuticals) is a selective agonist of the serotonin (5-hydroxytryptamine) 2C (5-HT2c) receptor.1 Qsymia (phentermine plus extended-release topiramate, Vivus) is a fixed-dose combination of the sympathomimetic amine phentermine, which is an anorectic agent, and the antiepileptic drug topiramate.2 Both medications reduce appetite and, in some people, induce a negative energy balance. In 1-year placebo-controlled clinical trials in which all participants received instruction in lifestyle modification, lorcaserin and phentermine–topiramate met one or both of the FDA criteria for clinically meaningful weight loss (see table).3 Moreover, as compared with the administration of placebo, drug treatment was genThe FDA’s Assessment of Two Drugs for Chronic Weight Management