Rimonabant in Obesity

1. RIO LIPIDS Trial Rimonabant in Obesity Presented at American College of Cardiology Scientific Sessions 2004 Presented by Dr. Jean-Pierre Despres

2. RIO LIPIDS Trial 1,036 patients with abdominal obesity and abnormal lipid profiles Randomized, double-blind, multicenter • Rimonabant • A selective cannabinoid type 1 receptor antagonist • 20 mg • n=346 • Rimonabant • A selective cannabinoid type 1 receptor antagonist • 5 mg • n=345 • Placebo • n=342 Treatment for 1 Year • Endpoints (1 year): • Weight loss 5% of body weight and 10% of body weight • Change in lipid profile Presented at ACC Scientific Sessions 2004

3. RIO LIPIDS Trial Weight Loss 5% p < 0.001 for high-dose vs placebo Weight Loss 10% p < 0.001 for high-dose vs placebo Presented at ACC Scientific Sessions 2004

4. RIO LIPIDS Trial Relative Reduction in CRP p=0.007 for rimonabant 20 mg vs placebo • C-reactive protein reduction greater in rimonabant 20 mg arm compared with placebo (from 3.7 to 2.7 mg/l with rimonabant 20 mg vs. 3.6 to 3.2 mg/l with placebo, p=0.007) • HDL increased 23% and triglycerides decreased 15% in rimonabant 20 mg, but no significant difference in LDL levels Presented at ACC Scientific Sessions 2004

5. RIO LIPIDS Trial • Among patients with abdominal obesity and abnormal lipid profiles, use of the selective cannabinoid type 1 receptor antagonist rimonabant in a 5 mg or 20 mg dose was associated with greater weight reduction after 1 year of treatment compared with placebo • Additional benefits were observed in HDL and triglyceride levels with rimonabant • Obesity is a growing epidemic, which has been shown to contribute to a variety of co-morbidities, including increased coronary heart disease, diabetes, and hyperlipidemia • Few pharmacologic agents have been identified as both safe and effective in reducing weight, pointing to the potential importance of the present study • Further evaluation is warranted