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

Background In animal models, cannabinoid-1 receptor (CB1) blockade produces a lean phenotype, with resistance to diet-induced obesity and associated dyslipidaemia. We assessed the effect of rimonabant, a selective CB1 blocker, on bodyweight and cardiovascular risk factors in overweight or obese patients.

Methods 1507 patients with body-mass index 30 kg/m2 or greater, or body-mass index greater than 27 kg/m2 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-totreat population.

Findings Weight 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]; p0·001 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 (p0·001) and 10% or greater (p0·001). 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. Interpretation CB1 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.