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
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.


RESULTS
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.


CONCLUSIONS
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.
Van Gaal
Luc F
LF
Department of Diabetology, Metabolism, and Clinical Nutrition, University Hospital Antwerp, Wilrijkstraat 10, 2650 Edegem-Antwerp, Belgium. luc.van.gall@uza.be
Rissanen
Aila M
AM
Scheen
André J
AJ
Ziegler
Olivier
O
Rössner
Stephan
S
D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D009767:Obesity, Morbid / Q000188:drug therapy; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D000077285:Rimonabant; D012307:Risk Factors; D049629:Waist-Hip Ratio; D015431:Weight Loss
D008055:Lipids; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077285:Rimonabant