Pharmacological therapy for obesity is in transition.

Historically,there have been few effective agents, and many have been with-drawn because of unacceptable side effects. Current options include three medications approved by the FDA for the treatment of obesity: phentermine, sibutramine and orlistat.

Phentermineand sibutramine suppress appetite and promote thermogenesis,and orlistat (Brand name: Xenical) blocks fat digestion and absorption in the gut.

Several drugs approved for other indications often promote orlistat, including Bupropion, metformin, topiramate and zonisamide; they have been used empirically for treatment of obesity and to counter the weight-promoting effects of other medications.

Expanding knowledge of the physiological mechanisms of body weight regulation has revealed new molecular targets, and more than 150 novel agents are under active development. Because weight regulation is complex, and redundant systems protect against perceived starvation, optimal treatment of obesity will likely require combinations of therapies. The accelerating emergence of new medications will facilitate the development of such effective combinations.

Massachusetts General Hospital Weight Center, Department of Medicine and Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, 50 Staniford Street, Boston, MA 02114, USA.