Internal Medicine News - Rimonabant enhanced weight loss success, improved lipids
Rimonabant, an investigational drug that is a cannabinoid-1 receptor blocker, promoted modest but sustained decreases in weight and waist circumference when combined with a low-calorie diet, reported Dr. F. Xavier Pi-Sunyer of the Obesity Research Center at St. Luke’s-Roosevelt Hospital, New York, and associates.
The drug also improved cardiometabolic risk factors in the multicenter Rimonabant in Obesity-North America (RIO-NA) trial, the researchers said.
Central cannabinoid-1 receptor activation stimulates appetite. Rimonabant reduces overactivation of these receptors both centrally and peripherally.
Related Results
Lancet, BMJ studies sound concern over anti-obesity drug rimonabantRimonabant improves cardiovascular risk profileRimonabant improves cardiovascular risk profileNew drug application for rimonabant pulledRimonabant weight loss sustained at 2 years
Rimonabant is under consideration at the Food and Drug Administration for two indications, weight management and smoking cessation. Sanofi Aventis, which would market the drug as Acomplia, announced last month that the company had received letters from the FDA saying that the weight management indication is “approvable,” but the smoking cessation indication is “nonapprovable.”
The RIO-NA study examined weight loss: Dr. Pi-Sunyer and associates assessed 3,045 obese or overweight individuals over 2 years at 64 U.S. and 8 Canadian clinical research centers.
All participants were instructed to follow a low-calorie diet and to increase their physical activity throughout the study.
They also were randomly assigned to take either 5 mg/day of rimonabant (1,216 subjects), 20 mg/day of rimonabant (1,222 subjects), or a placebo (607 subjects).
Only 51% of subjects in the low-dose rimonabant group, 55% in the high-dose rimonabant group, and 51% in the placebo group completed the first year of the study, the investigators said (JAMA 2006;295:761-75).
At that point, those participants who were taking either dosage of rimonabant showed a greater mean weight reduction and a greater mean decrease in waist circumference than participants taking placebo. The drug also decreased the prevalence of the metabolic syndrome.
The proportion of subjects who achieved a weight loss of 5% or more was 49% on high-dose rimonabant, 26% on low-dose rimonabant, and 20% on placebo.
Individuals who continued taking rimonabant for the second year of the study maintained a mean weight loss of 7.4 kg, while those who switched to placebo for the second year regained most of the weight they had lost. The same pattern held true for waist size.
After 2 years, 40% of the subjects taking high-dose rimonabant achieved a weight loss of 5% or greater, compared with 19% of those taking the placebo.
Compared with subjects who received placebo, those who took 20 mg of rimonabant showed favorable changes in levels of HDL cholesterol, triglycerides, fasting insulin, and insulin resistance, the researchers said.
These improvements “appeared to be approximately twice that expected from the achieved weight loss alone, suggesting a direct pharmacological effect of rimonabant on glucose and lipid metabolism beyond the weight loss achieved,” they reported.
In addition to the high dropout rate, the limited racial diversity of the study cohort, which predominantly involved white women, may diminish the generalizability of the study findings, the investigators added.
In an editorial comment, Dr. Denise G. Simons-Morton and associates at the National Heart, Lung, and Blood Institute, Bethesda, Md., said that the study had many strengths but “an overriding concern is the failure to obtain final weight measurements on about half of the randomized participants.”
“Randomization no longer serves its purpose when investigators fail to analyze those who do not adhere,” they said (JAMA 2006;295:826-8).
It would have been far more convincing to have analyzed actual data on the vast majority of those randomized,” Dr. Simons-Morton and her associates said.
In addition, the drug’s possible adverse effects must be studied in more detail. Dr. Pi-Sunyer and associates said rimonabant was “generally well tolerated, with adverse effects that were mostly mild and moderate.”
BY MARY ANN MOON
Contributing Writer
COPYRIGHT 2006 International Medical News Group
COPYRIGHT 2008 Gale, Cengage Learning
