Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO …

LF Van Gaal, AM Rissanen, AJ Scheen, O Ziegler… - The Lancet, 2005 - thelancet.com
LF Van Gaal, AM Rissanen, AJ Scheen, O Ziegler, S Rössner
The Lancet, 2005thelancet.com
Background In animal models, cannabinoid-1 receptor (CB 1) blockade produces a lean
phenotype, with resistance to diet-induced 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. Methods 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 …
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 −3ˇ4 kg [SD 5ˇ7]; p=0ˇ002 vs placebo) and 20 mg (−6ˇ6 kg [7ˇ2]; p<0ˇ001 vs placebo) compared with placebo (−1ˇ8 kg [6ˇ4]). Significantly more patients treated with rimonabant 20 mg than placebo achieved weight loss of 5% or greater (p<0ˇ001) and 10% or greater (p<0ˇ001). 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.
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