June 14, 2005

Bonnie Darves

June 14, 2005 (San Diego) - Final results of the yearlong RIO-Lipids trial of the novel selective CB 1 receptor endocannabinoid blocker rimonabant (Acomplia) suggest that the single-agent approach to treating multiple health issues associated with diabetes may soon become the standard. Rimonabant, the first in the new drug class of CB 1 blockers, was found to improve hemoglobin A1c (HbA1c) levels, reduce lipid levels and blood pressure, and reduce weight and waist size, researchers reported here at the American Diabetes Association's 65th Annual Scientific Sessions.

In patients who took the 20-mg dose of rimonabant, HbA1c dropped by 0.7% from baseline levels of 7.3%, and weight reduction and waist circumference were reduced 11.7 lb and 2 in, respectively, compared with those taking placebo. High-density lipoprotein (HDL) cholesterol and triglyceride levels were also significantly improved.

"This offers a new approach to the management of type 2 diabetes by addressing multiple cardioembolic risk factors," said principal investigator Andre Scheen, MD, PhD, head of clinical pharmacology in the division of diabetes, nutrition, and metabolic disorders at Academic Hospital of Liege in Belgium. "What was remarkable was the consistency of the movement of risk factors in the 20-mg [group]." Dr. Scheen also called the "clinically significant HbA1c improvement in a population that was already well controlled" an added benefit of the medication and one of the study's most noteworthy findings. In addition, 43% of patients taking the 20-mg dose achieved HbA1c levels below 6.5%.

The HDL increase was 15.4% in those taking the highest dose of the study drug, compared with 7.1% in the placebo group. The improvement in triglyceride levels in the patients receiving rimonabant was modest compared with placebo, at reductions of 9.1%and 7.3%, respectively. Blood pressure improvement occurred but did not reach statistical significance.

The phase 3 study, the fourth in a series of studies conducted in multiple European centers, included 1,045 obese patients with type 2 diabetes, whose mean age was 54 years and whose mean body mass index was 34 kg/m 2. Mean baseline HbA1c was 7.5%. The participants were randomized to receive either 20 mg (n = 315) or 5 mg (n = 303) of rimonabant or placebo (n = 317).

Adverse effects in patients receiving rimonabant were mostly mild and transient. The most common for patients taking the higher 20-mg dose were nausea, which affected 12.1% of patients, dizziness, and diarrhea. Hypoglycemia incidents occurred in 5.3% of patients receiving the 20-mg dose. A small number of patients also reported mood disturbances.

If risks and adverse effects are minimal and the safety and efficacy profiles seen in this study hold up in others, the multiple-target approach being used with drugs like rimonabant may represent a new era in diabetes risk-factor management, according to Richard Kahn, PhD, ADA's chief scientific and medical officer. "Ideally, you want a single drug that controls everything, and people really are looking to the 'poly pills' or 'poly-action' agents," Dr. Kahn says. "But of course it is not that simple. Rimonabant appears to be safe and well tolerated, but we need more experience with this [type of multiple-target] drug, and the fact that there were some mood disturbances may be a concern."

The study was funded by Sanofi-Aventis, the maker of rimonabant.

ADA 65th Annual Scientific Sessions: Abstract 7-LB. Presented June 12, 2005.

Reviewed by Gary D. Vogin, MD

Bonnie Darves is a freelance writer for Medscape.

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