Is rimonabant efficacious and safe in the treatment of obesity?

Background: The incidence of obesity is increasing worldwide, and in the USA approximately 100 million adults are overweight or obese. Orlistat and sibutramine are the drugs used at present for weight loss, but they both have a relatively modest effect. Objectives/methods: This evaluation is of the Rimonabant in Obesity (RIO) programme of clinical trials, and of the first trial to determine whether rimonabant has any effect on a clinical outcome. The Strategy to Reduce Atherosclerosis Development Involving Administration of Rimonabant -- the Intravascular Ultrasound Study (STRADIVARIUS) determined whether treatment with rimonabant decreased atherosclerosis. Results: The individual trials of the RIO programme showed that rimonabant 20 mg caused body weight loss, and also caused small decreases in waist circumference, plasma triglycerides and fasting glucose levels, and the incidence of the metabolic syndrome, while increasing levels of HDL cholesterol. Gastrointestinal side effects were the most common reported in the individual trials. However, when the five trials were combined, a small but significant increase in the incidence of depression and anxiety became apparent with rimonabant 20 mg. STRADIVARIUS showed that rimonabant 20 mg had no effect on atherosclerosis that was not progressing in subjects who were mostly also taking antithrombotic agents, statins, ß-blockers and angiotensin inhibitors. Conclusions: At present, it is doubtful whether the benefits of rimonabant outweigh the risks. Unless rimonabant is shown to have benefits in ongoing clinical outcome studies, there is little rationale to support its use in the treatment of obesity.