The first year results of the two-year trial Rimonabant In Obesity -- Europe (RIO-Europe), a Phase III clinical study comparing rimonabant, the first agent in a new therapeutic class known as selective cannabinoid type 1 (CB1) blockers, to placebo, were published today in The Lancet. The reported findings in overweight or obese patients taking rimonabant 20 mg once daily show a significant reduction in body weight, waist circumference -- a marker of intra-abdominal adiposity -- as well as improvements in insulin resistance and lipid and glucose profiles. The improvement in lipids (HDL-cholesterol and triglycerides) was shown to be partially independent from weight loss, suggesting a direct effect of rimonabant on these important metabolic cardiovascular risk parameters. The trial findings also revealed a decrease in the number of patients with metabolic syndrome(i) in the rimonabant 20 mg/day group.
Patients on rimonabant lost an extra 10 lbs over placebo, had higher HDL cholesterol, lower triglycerides, lower blood glucose, and lower insulin. All these are changes in healthy directions.
At one year, patients treated with rimonabant 20 mg/day lost an average of 14.55 lbs (p < 0.001 vs placebo) compared to 7.5 lbs for patients on rimonabant 5 mg/day (p = 0.002 vs placebo) and 3.97 lbs for those on placebo. Patients on rimonabant 20 mg/day also had an average decrease in their waist circumference of 2.56 inches (p < 0.001) versus 1.54 inches for those on rimonabant 5 mg (p = 0.002 vs placebo) and 0.94 inches for those on placebo.
Among patients completing the study, 67.4% of patients treated with rimonabant 20 mg/day lost more than 5% of their initial body weight (p < 0.001 vs placebo), compared to 44.2% of patients in the rimonabant 5 mg/day group (p = 0.001 vs placebo) and 30.5% in the placebo group. Moreover, 39% (p < 0.001 vs placebo) of patients on rimonabant 20 mg/day lost more than 10% of their initial body weight compared to 15.3% of those on rimonabant 5 mg/day and 12.4% of those on placebo.
The percentage of patients fulfilling the criteria for the metabolic syndrome was reduced by 54% after treatment with rimonabant 20 mg compared to 21% treated with placebo (p < 0.001). In addition to the reduction in weight and waist circumference, a statistically significant improvement in metabolic risk factors with rimonabant 20 mg vs. placebo was also observed. In patients treated for one year with rimonabant 20 mg/day, HDL-cholesterol (good cholesterol) increased by 22.3% (p < 0.001 vs placebo), compared to 16.2% (p = 0.005) in the rimonabant 5 mg/day group and 13.4% in the placebo group. Triglycerides were reduced by 6.8% in patients treated with rimonabant 20 mg (p < 0.001 vs placebo), compared to an increase of 5.7% and 8.3% in rimonabant 5 mg and placebo groups, respectively. Almost 50% of the rimonabant-induced changes in HDL-cholesterol and triglycerides were independent of the weight loss observed, suggesting a direct effect of the drug on lipid metabolism.
A significant reduction in fasting plasma glucose of 0.09 mmol/L was seen in patients treated with rimonabant 20 mg (p = 0.026 vs placebo) compared with an increase of 0.03 mmol/L in the placebo-treated group. A similar pattern was observed for insulin levels which decreased by 1.0 micron IU/mL in the rimonabant 20 mg group (p < 0.001 vs placebo) versus an increase of 1.8 micron IU/mL in the placebo-treated group. Finally, a decrease of 0.3% in HOMA-IR (a measure of insulin resistance) was seen in the rimonabant 20 mg group (p = 0.002 vs placebo) compared with an increase of 0.4% in the placebo-treated group.
Accomplia is made by the French pharmaceutical firm Sanofi-Aventis which is applying for licences to market it early in 2006 in Europe and the U.S. It is also known by its generic name Rimonabant.
Obesity contributes to heart disease, stroke, cancer, type II diabetes, and likely dozens of other diseases. A drug that reduces the incidence of obesity could substantially improve the long term health outlook for hundreds of millions of people. If no problems turn on Sanofi-Aventis stands to earn huge profits. But patients will receive the lion's share of the benefits from an effective and safe anti-obesity drug.
Rimonabant acts by blocking receptors in the endocannabinoid system, one of the body's pleasure centers -- the same class of centers affected by marijuana.
The drug, which has progressed to phase III development, works by blocking endogenous cannabinoid binding to neuronal CB1 receptors. Activation of these receptors by endoegenous cannabinoids, such as anadamide, increases appetite. It is the only endocannabinoid receptor antagonist in clinical development and thus offers a unique therapeutic approach to appetite control and weight reduction. The drug also has potential as a treatment for smoking cessation because the endocannabinoid system is also involved in the body's response to tobacco dependence.
As things stand now many people who give up smoking gain weight. With this drug smokers may be able to lose weight and stop smoking at the same time. Imagine if this drug works out as advertised. Millions of people will be skinnier and healthier and gain longer life expectancies.
|Share |||Randall Parker, 2005 April 15 03:44 PM Brain Appetite|