Weighing the options in the pharmacotherapy of obesity

In industrial nations the most common form of malnutrition is obesity. Obes ity is a chronic disease associated with increased morbidity and mortality. Unfortunately, the simplest treatment for obesity, increasing physical act ivity and reducing caloric intake, for the vast majority of patients is com pletely ineffective over the long term. Weight lost is quickly regained, an d body weights after intervention often exceed pretreatment levels. Early p harmacotherapy had been successful in reduction and maintenance of weight l oss; unfortunately, unforeseen side effects contributed to an unacceptable risk/benefit balance that necessitated the withdrawal of many of these agen ts. Current pharmacotherapy is limited, with only 2 compounds accepted for long-term use for the treatment of obesity. Both sibutramine and orlistat c ontribute to modest weight loss and maintenance and reduce obesity-associat ed risk factors. Beginning with the discovery of leptin in the mid-1990s, a renaissance in obesity research has taken place. This research has provide d more detailed insights into the regulation of energy homeostasis. The cen tral feedback regulation loops involving the leptin and melanocortinergic p athways have provided several targets for therapeutic intervention, includi ng leptin analogs and melanocortin agonists. Several peripheral targets inc luding uncoupling proteins and beta (3)-adrenergic receptor are also being explored for their anti-obesity potential. Therefore, it can be expected th at new pharmacotherapies will be available to help combat the epidemic of o besity.