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: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-to-treat 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]; 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. 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.
RCT Entities:
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 obesepatients. METHODS: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-to-treat 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]; 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. 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.
Authors: Mónica Alonso; Antonia Serrano; Margarita Vida; Ana Crespillo; Laura Hernandez-Folgado; Nadine Jagerovic; Pilar Goya; Carmen Reyes-Cabello; Vidal Perez-Valero; Juan Decara; Manuel Macías-González; Francisco Javier Bermúdez-Silva; Juan Suárez; Fernando Rodríguez de Fonseca; Francisco Javier Pavón Journal: Br J Pharmacol Date: 2012-04 Impact factor: 8.739
Authors: Basilio Moreno; Diego Bellido; Ignacio Sajoux; Albert Goday; Dolores Saavedra; Ana B Crujeiras; Felipe F Casanueva Journal: Endocrine Date: 2014-03-04 Impact factor: 3.633