The pharmacologic approach to the treatment of obesity.

Obesity is a major risk factor for morbidity and mortality, and a series of pharmacologic approaches are available for helping to manage the problem. Obesity is caused by an imbalance between caloric intake and energy expenditure, which is influenced by both environmental and genetic factors. Pharmacologic treatments include anorexigenic agents, which fall into two broad categories: those that act via brain catecholamine pathways and those that act via serotonin pathways. The most recent oral agents approved are dexfenfluramine, which is currently being marketed, and sibutramine. Both agents inhibit the control reuptake of serotonin but in addition may have effects on thermogenesis. Under investigation are agents that increase energy expenditure: the beta 3-adrenergic receptor agonists and drugs that prevent the intestinal absorption of free fatty acids and cholesterol. In development are innovative approaches to influence leptin and its receptors, various obesity genes, and biologic substances thought to influence satiety (neuropeptide Y, enterostatin, cholecystokinin, bombesin, and amylin). Obesity has now become a major target for drug development not only for affecting obesity per se but also for managing and preventing comorbid conditions such as diabetes and cardiovascular disease.