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

Lancet. 2005 Apr 16-22;365(9468):1389-97. doi: 10.1016/S0140-6736(05)66374-X.

Abstract

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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / prevention & control*
  • Double-Blind Method
  • Female
  • Humans
  • Insulin Resistance
  • Lipids / blood
  • Male
  • Middle Aged
  • Obesity / complications
  • Obesity / drug therapy*
  • Obesity / metabolism
  • Obesity, Morbid / drug therapy
  • Piperidines / adverse effects
  • Piperidines / therapeutic use*
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use*
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors*
  • Rimonabant
  • Risk Factors
  • Waist-Hip Ratio
  • Weight Loss*

Substances

  • Lipids
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • Rimonabant