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


RESULTS
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.


CONCLUSIONS
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.
Scheen
André J
AJ
Division of Diabetes, Nutrition and Metabolic Disorders, CHU Sart Tilman, University of Liege, Liege, Belgium. andre.scheen@chu.ulg.ac.be
Finer
Nick
N
Hollander
Priscilla
P
Jensen
Michael D
MD
Van Gaal
Luc F
LF
D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D063387:Cannabinoid Receptor Antagonists; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004361:Drug Tolerance; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000188:drug therapy; D050177:Overweight; D017060:Patient Satisfaction; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000077285:Rimonabant; D016896:Treatment Outcome
D001786:Blood Glucose; D063387:Cannabinoid Receptor Antagonists; D006442:Glycated Hemoglobin; D010880:Piperidines; D011720:Pyrazoles; D000077285:Rimonabant