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Presented at American College of Cardiology Scientific Sessions 2005 Presented by Dr. Luc Van Gaal

RIO EUROPE Trial. A Randomised Double-Blind Study of Weight Reducing Effect and Safety of Rimonabant in Obese Patients with or without Comorbidities. Presented at American College of Cardiology Scientific Sessions 2005 Presented by Dr. Luc Van Gaal. RIO EUROPE Trial.

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Presented at American College of Cardiology Scientific Sessions 2005 Presented by Dr. Luc Van Gaal

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  1. RIO EUROPE Trial A Randomised Double-Blind Study of Weight Reducing Effect and Safety of Rimonabant in Obese Patients with or without Comorbidities Presented at American College of Cardiology Scientific Sessions 2005 Presented by Dr. Luc Van Gaal

  2. RIO EUROPE Trial 1,507 patients with body mass index (BMI) ≥30 kg/m2, or BMI >27 kg/m2 with dyslipidemia or hypertension, and stable weight during the prior three months Randomized, Blinded, Parallel • Placebo • n=305 • Rimonabant • A selective cannabinoid type 1 receptor antagonist • 5 mg • n=603 • Rimonabant • A selective cannabinoid type 1 receptor antagonist • 20 mg • n=599 Treatment for 2 Years • Endpoints: • Primary: Absolute change in weight from baseline to one year. • Secondary: Weight loss relative to baseline weight (≥5% and ≥10%), waist circumference, and change in metabolic parameter. Presented at ACC Scientific Sessions 2004

  3. RIO EUROPE Trial Weight Loss at 2 Years Intent-To-Treat Analysis Weight Loss at 1 Year Weight Loss at 2 Years Patients who completed study duration p<0.001 p<0.001 p=0.038 p=0.0002 20mg Placebo 20mg 20mg 5mg Placebo Placebo 5mg 5mg • Weight loss at one year was greater in the rimonabant 20 mg group and the rimonabant 5 mg group than in the placebo group. • The weight loss results were maintained at 2 years,in an intent-to-treat analysis. • Among patients who completed the duration of the study, the weight loss at 2 years was even larger. • Mild side effects were higher in the 20 mg rimonabant group, including nausea, diarrhea, and dizziness, but were mostly mild and transient. Presented at ACC Scientific Sessions 2004

  4. RIO EUROPE Trial Loss of ≥10% Initial Body Weight at 1 Year Loss of ≥5% Initial Body Weight at 1 Year Loss of ≥10% Initial Body Weight at 2 Years p<0.001 p<0.001 p=0.002 20mg Placebo 20mg 20mg 5mg Placebo Placebo 5mg • Loss of ≥5% of initial body weight at 1 year was more frequent in both rimonabant arms compared with placebo, and similar results were reported for loss of ≥10% of initial body weight at 1 year and 2 years. • Waist circumference reduction at 1 year was greater in the rimonabant arms (8.5 cm for 20 mg and 5.3 cm for 5 mg) than placebo (4.5 cm; p<0.001 and p=0.002, respectively). • At 2 years, results were similar in the cohort of patients who completed the study (reduction of 7.5 cm in the 20 mg group, 5.3 cm in the 5 mg group, and 3.4 cm in the placebo group). Presented at ACC Scientific Sessions 2004

  5. RIO EUROPE Trial Triglycerides Reduction at 1 Year High Density Lipoprotein (HDL) Increase at 1 Year Metabolic Syndrome in 20mg Group p<0.001 vs. Placebo p<0.001 p<0.001 20mg Placebo 20mg Baseline 5mg Placebo 2 Yrs 5mg 1 Yr • Metabolic syndrome was reduced in the 20 mg rimonabant group at two years compared to placebo. • At one year, high-density lipoprotein (HDL) increased in the 20 mg rimonabant group versus placebo, and triglycerides were reduced. • Increases in HDL and reductions in triglycerides were maintained at 2 years. Both of these improvements were shown to be independent of weight loss. • Additionally, insulin response on oral glucose tolerance test at 1 year was improved in the 20 mg rimonabant group vs. placebo (reduction compared to baseline of 11.0 µU/ml vs. 2.3 µU/ml, p=0.019). Presented at ACC Scientific Sessions 2004

  6. RIO EUROPE Trial • Among obese patients, treatment with the cannabinoid type 1 receptor antagonist rimonabant was associated with a greater reduction in weight, waist circumference, and presence of metabolic syndrome through two years compared with placebo. • Both the present study and the RIO-LIIPIDS study demonstrated an improvement in lipids, as noted by higher HDL and lower triglycerides, a finding that was independent of weight reduction in the present study. • While some of the early benefit was lost, the majority of the weight loss, reduction in waist circumference and increase in HDL was maintained over the longer follow-up period.

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