Obesity pharmacology: past, present, and future.

Over the past several years, the pharmacologic treatment of obesity has undergone changes in safety, efficacy, and therapeutic targeting. The prevalence of cardiac valvulopathy associated with treatment with phentermine, fenfluramine, and dexfenfluramine is now becoming clarified with the publication of longer-term studies. Phenylpropanolamine, a well-known over-the-counter appetite suppressant, was recently removed from the market in the United States because of an increased risk of hemorrhagic stroke in women. In contrast, two currently approved medications, sibutramine and orlistat, have been shown to be safe and moderately effective for weight loss with documented beneficial effects on cardiovascular risk factors. Three other drugs, bupropion, topiramate, and ciliary neurotrophic factor, are undergoing clinical trials for obesity based on empirical observations. Most promising are the advances in genetics and molecular biology that are beginning to elucidate new targets for controlling appetite and energy utilization. These therapeutic agents will likely herald a second generation of anti-obesity medications over the next decade.