Early results of the RIO-Lipids trial using a new molecule, rimonabant, have been presented at the last American College of Cardiology meeting held in New Orleans by the principal investigator of the study, Dr. Jean-Pierre Després from the Laval Hospital Research Center. Rimonabant is the first selective cannabinoid type 1 (CB1) receptor blocker developed for the treatment of obesity and smoking cessation. The RIO-Lipids study tested the ability of rimonabant to reduce body weight in overweight or obese (BMI 27-40 kg/m2) patients with untreated dyslipidemia. One-year treatment with rimonabant 20 mg induced a significant reduction in both body weight (-6.9 kg) and abdominal obesity as estimated by waist circumference (-9.1 cm), which were greater than in the placebo group (p<0.001). Significant improvements in the plasma lipoprotein-lipid profile compared to placebo (p<0.001) were also achieved with rimonabant 20 mg, which included reduction in plasma triglyceride levels (-15%) and an increase in HDL cholesterol concentration (+23%) leading to a substantial reduction in the total cholesterol/HDL cholesterol ratio (-0.72 unit). However, rimonabant had no effect on LDL-cholesterol levels.

The impact of rimonabant therapy on electrophoretic characteristics of LDL was also investigated in the RIO-Lipids trial. Mean change in LDL peak particle diameter induced by rimonabant 20 mg was significantly different from what observed in the placebo group (+1.2 Å, p<0.001). Furthermore, the distribution of LDL particle sizes was altered as a decrease in the proportion of atherogenic small LDL (-4.7%, p=0.002) and an increase in the percentage of large LDL particles (+6.3%, p<0.001) were observed with rimonabant 20 mg therapy. The 75 g oral glucose tolerance test conducted on all subjects revealed that as compared to placebo, rimonabant 20 mg improved in vivo insulin sensitivity. Furthermore, the prevalence of patients with the Metabolic Syndrome as defined by the NCEP-ATP III criteria was reduced from 52.9% to 25.8% among patients treated with rimonabant 20 mg (Figure). In addition, CRP was significantly reduced by 27% with rimonabant 20 mg compared to only 11% in the placebo group (p=0.007).

Overall, these results suggest that Rimonabant therapy would be an effective additional pharmacological approach to target a critical determinant of the Metabolic Syndrome: abdominal obesity which can be simply detected in clinical practice by an expanded waistline.