Rimonabant: Sustained Weight Loss, Improved Blood Profiles
Taking the investigational drug rimonabant (brand name Acomplia) produces modest, sustained weight loss and improved blood markers after two years, according to a report published in the February 15 issue of the Journal of the American Medical Association.
In addition to losing weight, study participants taking rimonabant also showed improved high-density lipoprotein (HDL) cholesterol and triglyceride levels at the two-year mark.
About two-thirds of Americans are overweight or obese, according to authors F Xavier Pi-Sunyer, MD, of the Obesity Research Center, St Luke's-Roosevelt Hospital, New York, and colleagues. This excess weight greatly increases the risk of developing diabetes mellitus and heart disease and death from related causes. For this reason, researchers believe, obesity-management goals should include not only weight-loss (particularly around the waist), but also the improvement of cardio-metabolic risk factors, including abnormal cholesterol and blood sugar levels.
In a randomized, double-blind, placebo-controlled study, Dr Pi-Sunyer and colleagues evaluated investigational drug rimonabant's efficacy and safety, when taken in conjunction with diet and exercise. Study endpoints included reduction in body weight and waist circumference, long-term weight maintenance and reduction of cardiometabolic risk factors in obese and higher-risk overweight patients.
The study was conducted from August 2001 to April 2004 and included 3,045 obese adult participants (body mass index or "BMI" = 30 or more) or overweight (BMI > 27 plus high blood pressure or dyslipidemia).
Patients were randomized to receive rimonabant (5 mg/day), rimonabant (20 mg/day) or placebo for one year. At one year, patients receiving rimonabant were then re-randomized to receive placebo or to continue to receive rimonabant at the same dose; the placebo group continued to receive placebo during year two.
Completing the first year of the study were:
- 51% of participants receiving rimonabant (5 mg/day)
- 55% of participants receiving rimonabant (20 mg/day)
- 51% of participants receiving placebo.
At one year, participants receiving either dose of rimonabant had significantly greater weight loss than participants receiving placebo. At this time, the percentage of participants who achieved at least a 5% weight loss was:
- 26.1% for patients receiving rimonabant (5 mg/day)
- 48.6% for patients receiving rimonabant (20 mg/day)
- 20.0% for patients receiving placebo.
Participants receiving rimonabant (20 mg/day) had greater average reductions in weight, waist circumference and triglycerides, as well as a greater increase in HDL cholesterol.
Participants who were switched from the higher dose of rimonabant to placebo during the second year experienced weight regain, whereas those who continued to receive 20 mg/day maintained both their weight loss and improved cardiometabolic risk factors.
Rimonabant was generally well tolerated, with the most common drug-related adverse event being nausea (11.2% for participants receiving rimonabant (20 mg/day) versus 5.8% for the placebo group).
"It must be acknowledged that the trial was limited by a high dropout rate and that long-term effects of the drug require further study. Still, our observations collectively suggest that rimonabant may well represent an innovative approach to the management of multiple cardiometabolic risk factors, facilitating and maintaining improvements through weight loss-dependent and-independent pathways," the authors conclude.
Effect of Rimonabant, a Cannabinoid-1 Receptor Blocker, on Weight and Cardiometabolic Risk Factors in Overweight or Obese Patients. RIO-North America: A Randomized Controlled Trial. Xavier Pi-Sunyer, MD, et al, Journal of the American Medical Association, volume 295, pages 761-775, February 14, 2006.
Posted: February 2006