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The Role of Endocannabinoid System Blockade in the Treatment of the Metabolic Syndrome

From the Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece (Dr Kakafika, Dr Karagiannis, Dr Athyros) and the Department of Clinical Biochemistry (Vascular Prevention Clinic), Royal Free Hospital, Royal Free University College Medical School (University of London), London, UK (Dr Mikhailidis).

This review considers the use of the first selective blocker of the cannabinoid receptor type 1, rimonabant, to reduce weight and improve cardiovascular disease risk factors in obese patients with metabolic syndrome or multiple cardiovascular disease risk factors. In 4 large trials—Rimonabant in Obesity (RIO)-Lipids, RIO-Europe, RIO-North America, and RIO-Diabetes—after 1 to 2 years of treatment, rimonabant (20 mg/day) led to a significantly greater weight loss and reduction in waist circumference compared with placebo. Treatment with rimonabant was also associated with other favorable changes, including better glycemic control in type 2 diabetes mellitus, improved lipid profile, reduced blood pressure, increased adiponectin levels, fall in high-sensitivity C-reactive protein concentrations, and an overall decrease in the prevalence of the metabolic syndrome. Initial experience with rimonabant shows that it is generally well tolerated with the most common side effect of mild nausea. Rimonabant may be a useful adjunct to lifestyle and behavior modification in the treatment of obese subjects with metabolic syndrome or multiple cardiometabolic risk factors.

Key Words: Rimonabant • metabolic syndrome • cardiovascular risk factors • obesity • lipoproteins

Address for reprints: Address for correspondence: Dimitri P. Mikhailidis, MD, FFPM, FRCP, FRCPath, Department of Clinical Biochemistry, Royal Free Hospital, Royal Free University College School of Medicine, Pond Street, London NW3 2QG, United Kingdom; e-mail: MIKHAILIDIS{at}aol.com.

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				J. Rosenstock, P. Hollander, S. Chevalier, A. Iranmanesh, and for the SERENADE Study Group SERENADE: The Study Evaluating Rimonabant Efficacy in Drug-Naive Diabetic Patients: Effects of monotherapy with rimonabant, the first selective CB1 receptor antagonist, on glycemic control, body weight, and lipid profile in drug-naive type 2 diabetes Diabetes Care, November 1, 2008; 31(11): 2169 - 2176. [Abstract] [Full Text] [PDF]