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

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.

• Authors: André J Scheen, Nick Finer, Priscilla Hollander, Michael D Jensen, Luc F Van Gaal, RIO-Diabetes Study Group
• Journal: Lancet (London, England) (Lancet) Vol. 368 Issue 9548 Pg. 1660-72 (Nov 11 2006) ISSN: 1474-547X [Electronic] England
• PMID: 17098084 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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