First year results of the two year trial Rimonabant In Obesity - Europe (RIO-Europe), a Phase III clinical study comparing placebo to rimonabant, the first agent in a new therapeutic class known as selective cannabinoid type 1 (CB1) blockers, showed that overweight or obese people taking rimonabant 20mg once daily benefited from a significant reduction in their body weight, waist circumference – a marker of the dangerous abdominal obesity - and improvements in their lipid and glycemic profiles.
The improvement in lipids (HDL-cholesterol and triglycerides) was demonstrated to be partially independent from weight loss, implying a direct effect of the drug on these important metabolic cardiovascular risk parameters. The trial findings also revealed a significant decrease in the percentage of patients with metabolic syndrome1 in the rimonabant 20 mg/day group compared to placebo. These new results from the RIO-Europe study confirm rimonabant’s potential to become an important tool in the reduction of cardiovascular risk factors by lowering body weight, improving metabolic syndrome-associated parameters in overweight/obese subjects and aiding in smoking cessation as presented earlier this year.
RIO Europe, an international, multicentre, randomized, double-blind, placebo-controlled, parallel-group study compared rimonabant 20mg/day and 5mg/day to placebo in 1,507 overweight/obese patients (Body Mass Index (BMI) ? 30 kg/m2 or BMI > 27 with co-morbidity (e.g. dyslipidemia, hypertension) in 60 centres across Europe (Belgium, Finland, France, Germany, the Netherlands, Sweden) and the United States for a period of 2 years. The announcement made at the ESC 2004 concerns the first year data of the study.
Patients treated for one year with rimonabant 20mg/day lost an average of 8.6kg (about 19 lbs) (p<0.001 vs placebo) compared to 4.8kg (about 11 lbs)for patients on rimonabant 5mg/day (p=0.038 vs placebo) and 3.6kg (about 8 lbs) for those on placebo. Nearly 70% of patients treated with rimonabant 20mg/day lost more than 5% of their initial body weight (p< 0.001 vs placebo), compared to 44.2% of patients in the rimonabant 5mg/day group (p=0.002 vs placebo) and 30.5% in the placebo group. Moreover, 39% (p<0.001 vs placebo) of patients on rimonabant 20mg/day lost more than 10% of their initial body weight compared to 15.3% of those on rimonabant 5mg/day and 12.4% of those on placebo.
Patients on rimonabant 20mg/day also had an average decrease in their waist circumference of 8.5 cm (about 3.5 inches) (p< 0.001) versus 5.3 cm (2 inches) for those on rimonabant 5mg (p=0.002 vs placebo) and 4.5 cm (about 1.5 inches) for those on placebo.
The number of patients diagnosed as having metabolic syndrome at baseline (42.2%) was reduced by more than half (19.6%) after treatment with rimonabant 20mg (p<0.001 compared to placebo).
In addition to weight loss, a statistically significant improvement in metabolic risk factors with rimonabant 20mg vs. placebo was also observed.
In patients treated for one year with rimonabant 20 mg/day, HDL-cholesterol (good cholesterol) increased by 27.0% (p< 0.001 vs placebo), compared to 19% in the rimonabant 5mg/day group and 17.3% in the placebo group. Weight loss accounted for only approximately half the improvement in HDL seen with rimonabant 20mg vs. placebo, implying a significant direct effect of the drug on lipid metabolism, independent of weight loss (p=0.005).
In patients treated for one year with rimonabant 20mg, triglycerides were reduced by 10.6% in patients on rimonabant 20 mg (p < 0.001 vs. placebo), while increasing by 4.9% for rimonabant 5mg and by 6.6% for placebo.
As seen with HDL, weight loss accounted for only approximately half the improvement in triglycerides seen with rimonabant 20mg vs. placebo, implying a significant direct effect of the drug on lipid metabolism, independent of weight loss (p=0.005).
An improved insulin response as demonstrated by an Oral Glucose Tolerance Test was also observed. During the 2 hour test, patients on rimonabant 20 mg had to produce less insulin to metabolize their glucose compared to those on placebo (reduction by 11.0 µIU/ml vs baseline compared to 2.3 µIU/ml in the placebo group;p=0.019 ).