Weighing the options in the pharmacotherapy of obesity

In industrial nations the most common form of malnutrition is obesity. Obesity is a chronic disease associated with increased morbidity and mortality. Unfortunately, the simplest treatment for obesity, increasing physical activity and reducing caloric intake, for the vast majority of patients is completely ineffective over the long term. Weight lost is quickly regained, and body weights after intervention often exceed pretreatment levels. Early pharmacotherapy had been successful in reduction and maintenance of weight loss; unfortunately, unforeseen side effects contributed to an unacceptable risk/benefit balance that necessitated the withdrawal of many of these agents. Current pharmacotherapy is limited, with only 2 compounds accepted for long-term use for the treatment of obesity. Both sibutramine and orlistat contribute to modest weight loss and maintenance and reduce obesity-associated risk factors. Beginning with the discovery of leptin in the mid-1990s, a renaissance in obesity research has taken place. This research has provided more detailed insights into the regulation of energy homeostasis. The central feedback regulation loops involving the leptin and melanocortinergic pathways have provided several targets for therapeutic intervention, including leptin analogs and melanocortin agonists. Several peripheral targets including uncoupling proteins and beta3-adrenergic receptor are also being explored for their anti-obesity potential. Therefore, it can be expected that new pharmacotherapies will be available to help combat the epidemic of obesity.