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Effects of the Cannabinoid-1 Receptor Blocker Rimonabant on Weight Reduction and Cardiovascular Risk Factors in Overweight Patients: 1-Year Experience From the RIO-Europe Study

2005; Elsevier BV; Volume: 14; Issue: 7 Linguagem: Inglês

10.1016/j.accreview.2005.06.021

1879-2065

Luc F. Van Gaal, Aila Rissanen, André Scheen, Olivier Ziegler, Stephan Rössner,

Diet, Metabolism, and Disease

BackgroundIn animal models, cannabinoid-1 receptor (CBB 1 ) blockade produces a lean phenotype, with resistance to dietinduced obesity and associated dyslipidaemia.We assessed the effect of rimonabant, a selective CB 1 blocker, on bodyweight and cardiovascular risk factors in overweight or obese patients. Methods1507 patients with body-mass index 30 kg/m 2 or greater, or body-mass index greater than 27 kg/m 2 with treated or untreated dyslipidaemia, hypertension, or both, were randomised to receive double-blind treatment with placebo, 5 mg rimonabant, or 20 mg rimonabant once daily in addition to a mild hypocaloric diet (600 kcal/day deficit).The primary efficacy endpoint was weight change from baseline after 1 year of treatment in the intention-to-treat population. FindingsWeight loss at 1 year was significantly greater in patients treated with rimonabant 5 mg (mean -3 • 4 kg [SD 5•7]; p=0•002 vs placebo) and 20 mg (-6•6 kg [7•2]; p<0•001 vs placebo) compared with placebo (-1•8 kg [6•4]).Significantly more patients treated with rimonabant 20 mg than placebo achieved weight loss of 5% or greater (p<0•001) and 10% or greater (p<0•001).Rimonabant 20 mg produced significantly greater improvements than placebo in waist circumference, HDL-cholesterol, triglycerides, and insulin resistance, and prevalence of the metabolic syndrome.The effects of rimonabant 5 mg were of less clinical significance.Rimonabant was generally well tolerated with mild and transient side effects. InterpretationCB 1 blockade with rimonabant 20 mg, combined with a hypocaloric diet over 1 year, promoted significant decrease of bodyweight and waist circumference, and improvement in cardiovascular risk factors.