Long-term effect of CB1 blockade with rimonabant on cardiometabolic risk factors: two year results from the RIO-Europe Study

Eur Heart J. 2008 Jul;29(14):1761-71. doi: 10.1093/eurheartj/ehn076. Epub 2008 Apr 15.

Abstract

Aims: Rimonabant, the first selective cannabinoid type 1 receptor blocker, has been shown to produce weight loss and improvements in several cardiometabolic risk factors over 1 year. We report the 2 year efficacy and tolerability data of rimonabant.

Methods and results: Patients with a body mass index > or =30 or >27 kg/m(2) with treated/untreated hypertension, dyslipidaemia, or both, were randomized to double-blind treatment with placebo, rimonabant 5 or 20 mg once daily plus a calorie-restricted diet for 2 years. Weight loss from baseline to 2 years in the intention-to-treat population was significantly greater with rimonabant 20 mg (mean +/- SD: -5.5 +/- 7.7 kg; P < 0.001) and 5 mg (-2.9 +/- 6.5 kg; P = 0.002) than placebo (-1.2 +/- 6.8 kg). Rimonabant 20 mg produced significantly greater improvements than placebo in waist circumference, high-density lipoprotein cholesterol, triglycerides, fasting glucose and insulin levels, insulin resistance, and metabolic syndrome prevalence. Rimonabant 20 mg produced clinically meaningful improvements in all Impact of Weight on Quality of Life-Lite questionnaire domain scores at 2 years. Rimonabant was generally well tolerated and rates of adverse events, including depressed mood disorders and disturbances were similar to placebo during year 2. Proportions of patients with clinically significant depression (Hospital Anxiety and Depression Scale score >11) were similar in all treatment groups.

Conclusion: Rimonabant 20 mg over 2 years promoted clinically relevant and durable weight loss and improvements in cardiometabolic risk factors.

Trial registration: ClinicalTrials.gov NCT00386061.

Publication types

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

MeSH terms

  • Adult
  • Anti-Obesity Agents / adverse effects
  • Anti-Obesity Agents / therapeutic use*
  • Blood Glucose / metabolism
  • Body Mass Index
  • Cannabinoid Receptor Antagonists*
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / prevention & control*
  • Cholesterol, HDL / blood
  • Dose-Response Relationship, Drug
  • Epidemiologic Methods
  • Female
  • Humans
  • Insulin / blood
  • Male
  • Metabolic Syndrome / prevention & control
  • Middle Aged
  • Obesity / blood
  • Obesity / drug therapy*
  • Obesity / physiopathology
  • Piperidines / adverse effects
  • Piperidines / therapeutic use*
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use*
  • Rimonabant
  • Treatment Outcome
  • Triglycerides / blood
  • Weight Loss / drug effects

Substances

  • Anti-Obesity Agents
  • Blood Glucose
  • Cannabinoid Receptor Antagonists
  • Cholesterol, HDL
  • Insulin
  • Piperidines
  • Pyrazoles
  • Triglycerides
  • Rimonabant

Associated data

  • ClinicalTrials.gov/NCT00386061