Current and novel approaches to the drug therapy of obesity

Introduction: Obesity has been described as the greatest current threat to human health. Although diet and lifestyle changes remain the cornerstones of therapy for obesity, weight losses are often small, and long-term success is disappointing. Discussion: When these lifestyle-modifying attempts fail, the use of anti-obesity drugs is warranted. Drug treatment is often indicated, but is somewhat limited by the minimal number of well-tolerated drugs that have proven to have long-term efficacy in maintaining body weight loss. The currently available drugs, sibutramine and orlistat, appear modestly effective in promoting weight loss. However, pharmacological therapy for obesity is in transition; 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. Conclusions: Because weight regulation is complex, and redundant systems protect against perceived starvation, optimal treatment of obesity will likely require combinations of therapies. In addition, a better comprehension of the problem prior to its treatment would be preferable before targeting homeostatic pathways which could be irrelevant.