Drug treatment for obesity in the post-sibutramine era

Obesity is a major health problem worldwide. It is associated with cardiovascular diseases, diabetes mellitus and decreased longevity. In managing obesity, diet and exercise are essential; pharmacological therapy may be added for obese patients or overweight patients with cardiovascular risk factors. Sibutramine is a serotonergic and adrenergic drug that reduces food intake and increases thermogenesis. It reduces bodyweight by about 4.2 kg after 12 months, and improves blood glucose and lipids; however, it can increase heart rate and blood pressure. In the SCOUT (Sibutramine Cardiovascular OUTcomes) study, sibutramine increased serious cardiovascular events, such as stroke or myocardial infarction, compared with placebo, and was consequently withdrawn from the market. The lesson learnt from this is the importance of patient selection, limiting the duration of treatment and stopping treatment in non-responders. Currently, phentermine and amfepramone (diethylpropion) are approved for short-term treatment of obesity (up to 3 months) and orlistat is approved for longer-term treatment; however, the gastrointestinal adverse effects of orlistat may be intolerable for some patients. There is now a clear need to find anti-obesity drugs that are effective and safe in the long term.