Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study

Lancet. 2006 Nov 11;368(9548):1660-72. doi: 10.1016/S0140-6736(06)69571-8.

Abstract

Background: Rimonabant, a selective cannabinoid type 1 receptor blocker, reduces bodyweight and improves cardiovascular and metabolic risk factors in non-diabetic overweight or obese patients. The aim of the RIO-Diabetes trial was to assess the efficacy and safety of rimonabant in overweight or obese patients with type 2 diabetes that was inadequately controlled by metformin or sulphonylureas.

Methods: 1047 overweight or obese type 2 diabetes patients (body-mass index 27-40 kg/m2) with a haemoglobin A1c (HbA1c) concentration of 6.5-10.0% (mean 7.3% [SD 0.9] at baseline) already on metformin or sulphonylurea monotherapy were given a mild hypocaloric diet and advice for increased physical activity, and randomly assigned placebo (n=348), 5 mg/day rimonabant (360) or 20 mg/day rimonabant (339) for 1 year. Two individuals in the 5 mg/day group did not receive double-blind treatment and were thus not included in the final analysis. The primary endpoint was weight change from baseline after 1 year of treatment. Analyses were done on an intention-to-treat basis. This trial is registered at ClinicalTrials.gov, number NCT00029848.

Findings: 692 patients completed the 1 year follow-up; numbers in each group after 1 year were much the same. Weight loss was significantly greater after 1 year in both rimonabant groups than in the placebo group (placebo: -1.4 kg [SD 3.6]; 5 mg/day: -2.3 kg [4.2], p=0.01 vs placebo; 20 mg/day: -5.3 kg [5.2], p<0.0001 vs placebo). Rimonabant was generally well tolerated. The incidence of adverse events that led to discontinuation was slightly greater in the 20 mg/day rimonabant group, mainly due to depressed mood disorders, nausea, and dizziness.

Interpretation: These data indicate that 20 mg/day rimonabant, in combination with diet and exercise, can produce a clinically meaningful reduction in bodyweight and improve HbA1c and a number of cardiovascular and metabolic risk factors in overweight or obese patients with type 2 diabetes inadequately controlled by metformin or sulphonylureas.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Blood Glucose / drug effects
  • Cannabinoid Receptor Antagonists
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / etiology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Tolerance
  • Female
  • Glycated Hemoglobin A / drug effects
  • Humans
  • Male
  • Middle Aged
  • Obesity / complications
  • Obesity / drug therapy
  • Overweight
  • Patient Satisfaction
  • Piperidines / administration & dosage
  • Piperidines / pharmacology
  • Piperidines / therapeutic use*
  • Pyrazoles / administration & dosage
  • Pyrazoles / pharmacology
  • Pyrazoles / therapeutic use*
  • Rimonabant
  • Treatment Outcome

Substances

  • Blood Glucose
  • Cannabinoid Receptor Antagonists
  • Glycated Hemoglobin A
  • Piperidines
  • Pyrazoles
  • Rimonabant

Associated data

  • ClinicalTrials.gov/NCT00029848