The therapeutic cupboard containing antiobesity drugs has never been well stocked. The European Medicines Agency (EMA) recently decided that sibutramine must follow the example of rimonabant, withdrawn last year because of safety concerns.1 This leaves just one drug—orlistat—to face the rising tide of obesity across the continent. The demise of sibutramine carries both irony and wider messages for the management of obesity.

Sibutramine fell at the crucial hurdle of cardiovascular risk. Arterial disease—which leads ultimately to myocardial ischaemia, heart failure, and stroke—affects most obese people to some degree and is their major cause of death.2 Much evidence suggests that weight loss decreases morbidity and mortality associated with cardiovascular disease,3 and this is an important justification for all antiobesity measures, including drugs. Unfortunately for sibutramine, an interim analysis of the SCOUT (Sibutramine Cardiovascular Outcome Trial) study found that the drug increased morbidity from cardiovascular disease.1

The odds were always stacked against sibutramine, because cardiovascular risk is embedded in its mechanism of action. Sibutramine acts centrally to reduce food intake; it inhibits the presynaptic reuptake and degradation of serotonin and noradrenaline, thus enhancing the appetite suppressing actions of both neurotransmitters. …