Rimonabant Improves Atherogenic Lipid Profile, Reduces Visceral Fat: Presented at EAS

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Title: Rimonabant Improves Atherogenic Lipid Profile, Reduces Visceral Fat: Presented at EAS
URL: http://www.pslgroup.com/dg/220782.htm
Doctor's Guide
May 1, 2008

By Sara Freeman

ISTANBUL, Turkey -- April 30, 2008 -- Rimonabant therapy in combination consumption of a low-calorie diet improves both the quality and quantity of high-density lipoprotein cholesterol (HDL-C), and decreases triglycerides and visceral fat in initially weight-stable patients who are centrally obese with atherogenic lipid profiles.

These data, from An International Study of Rimonabant in Dyslipidemia With Atherogenic Risk In Abdominally Obese Patients (ADAGIO-LIPIDS) and a computed tomography (CT) imaging substudy were presented here during a late-breaking session at the 77th European Atherosclerosis Society Congress (EAS).

The study, presented on April 29, was a 1-year, randomised, double-blind trial performed at 6 centres in Canada that was a follow-on from the Rimonabant in Obesity-Lipids (RIO-LIPIDS) trial.

The ADAGIO-LIPIDS trial aimed to answer some questions raised by the RIO-LIPIDS results, explained principal investigator Jean-Pierre Després, MD, Director, Lipid Research Centre, Université Laval, Quebec, Quebec, Canada.

Results from the RIO-LIPDIS trial had demonstrated a dramatic increase in HDL-C levels. Dr. Després said that a key aim of the trial was to assess the effect of rimonabant on HDL-C in initially weight-stable patients because they had already lost weight in the run-in phase, "which was probably an artifact."

The CT imaging substudy was designed to determine the effect of rimonabant on visceral fat, based on previous evidence which showed that the drug appeared to reduce patients' waistlines.

After a 1-week screening period, 799 patients were randomised to rimonabant 20 mg daily (n = 404) or placebo (n = 395) for 1 year. All patients were also given dietary advice and asked to undertake a moderate-calorie diet (600 kcal/day).

Results showed that rimonabant increased HDL-C by 7.37% and decreased triglycerides by 17.90% by the end of the study. Both results were highly statistically significant compared with placebo (P < .0001).

Although there was no change in the overall level of low-density lipoprotein cholesterol (LDL-C) between the 2 treatment groups, there was a much lower proportion of small as compared with large LDL particles in rimonabant-treated patients.

Rimonabant was also associated with a 0.9% increase in HDL particle size, and an increase in levels of both HDL2 (+52.6% vs placebo; P < .03) and HDL3 (+4.3% vs placebo; P < .01) subfractions.

A decrease in the apo B/apo A-I ratio was noted, as well as in levels of high-sensitivity C-reactive protein. There was a very significant increase in adiponectin levels compared with placebo, with a mean increase of 18.9% (P < .0001).

"We found improvements in all studied features of the metabolic syndrome, including blood pressure," said Dr. Després. Safety was also confirmed, he said, with no significant difference in levels of depression or depressed mood compared with placebo.

In a presentation following Dr. Després, coprincipal investigator Robert Ross, PhD, Research Chair, School of Kinesiology and Health Studies, Department of Medicine, Queen's University, Kingston, Ontario, Canada, presented the results of the CT imaging substudy.

The substudy compared baseline with 12-month assessments and showed significantly less adipose tissue in patients treated with rimonabant than in patients in the placebo group (-12.2% vs -5.2%; P = .0003). Both visceral (-10.08% vs placebo) and subcutaneous (-5.07% vs placebo) adipose tissue were significantly lower with active therapy (P = .0003 and P = .0043, respectively).

These findings were anticipated, Dr. Ross said.

There is an arsenal of pharmacotherapies targeting cardiovascular risk factors but so far none have addressed the root cause of the metabolic syndrome -- excess visceral fat.

"We're very encouraged that, for the first time in a very high-risk group, an antagonist of the endocannabinoid system actually treats the root cause," he concluded.

Funding for ADAGIO-LIPIDS was provided by sanofi-aventis.

[Presentation titles: Rimonabant Reduces Both Intra-Abdominal Adiposity and Liver Fat and Improves Cardiometabolic Risk Factors: The ADAGIO-LIPIDS Trial. Effects of Rimonabant on Intra-Abdominal Adiposity and Liver Fat: The ADAGIO-LIPIDS Computed Tomography Substudy. Late-Breaking Abstracts]

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