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Up to Half of Metabolic Improvement Seen With Rimonabant Is Attributable to Drug Rather Than Weight-Loss Alone: Presented at ACC

By Olwen Glynn Owen

ATLANTA, G.A. -- March 15, 2006 -- How patients lose weight can make a substantial difference to their associated cardiometabolic risk factors such as dyslipidemia and glycated hemoglobin levels, researchers reported here.

In data presented here on March 15^th at the 55^th Annual Scientific Session of the American College of Cardiology (ACC), researchers compared the relative metabolic benefits of losing weight while taking placebo against the investigational selective cannabinoid type 1 (CB1) receptor blocker rimonabant.

Rimonabant targets the endocannabinoid system blocking CB1 receptors expressed in the central nervous system and peripherally in adipocytes, liver, muscle cells, and other tissues. In obese individuals, receptors are overactivated, stimulating appetite, increasing food intake, and also influencing lipid and glucose metabolism.

In patients taking rimonabant, up to half of the improvement seen in some metabolic parameters is attributable to direct effects of rimonabant therapy rather than to the weight loss it causes, researchers say.

Xavier Pi-Sunyer, MD, director, Obesity Research Center, chief of endocrinology, diabetes, and nutrition, St. Luke's-Roosevelt Hospital, and professor of medicine, College of Physicians and Surgeons, Columbia University, New York, New York, and colleagues presented pooled data from 4 clinical trials that are part of the Rimonabant in Obesity and Related Metabolic Disorders (RIO) program. The trials are RIO-Lipids, RIO-Diabetes, RIO-North America, and RIO-Europe

Prespecified analyses of the data compared the effects of placebo and rimonabant on levels of high-density lipoprotein (HDL) cholesterol, triglycerides, fasting insulin, hemoglobin A1c (HbA1c), and adiponectin, where patients achieved the same percentage weight loss.

"In the RIO-lipids trial, HDL was consistently increased and triglycerides reduced to a greater extent with rimonabant than with placebo," Dr Pi-Sunyer noted. "For any level of weight loss, rimonabant achieved an additional improvement in lipid profile. In RIO-diabetes, HBA1c was consistently and significantly reduced more by rimonabant."

The percentage overall increase in HDL attributable to rimonabant over weight loss alone was 45%, while for adiponectin it was 57%. For the reductions seen in triglycerides, fasting insulin, and HbA1c, it was 46%, 49%, and 55%, respectively.

"This analysis illustrates the weight-dependent and weight-independent effects of CB1 receptor blockade," Dr. Pi-Sunyer concluded. "It suggests rimonabant has an additional independent benefit at any level of weight loss."

Commenting on the results, Julian Halcox, MD, vascular physiologist and cardiologist, University College, London, United Kingdom, said rimonabant appears to reduce abdominal fat faster than could be achieved by diet and exercise. "However, despite the apparent added value of rimonabant weight loss, it is important to continue to focus on the need to adopt healthy lifestyle behaviors," he stressed.


[Presentation title: Improvement of Metabolic Parameters With Rimonabant Beyond the Effect Attributable to Weight Loss Alone: Pooled One-Year Data From the RIO (Rimonabant in Obesity and Related Metabolic Disorders) Program. Abstract 849-3]

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