CB1 receptor blockade and its impact on cardiometabolic risk factors: overview of the RIO programme with rimonabant.

Algorithms; Anti-Obesity Agents/adverse effects/therapeutic use; Cardiovascular Diseases/etiology; Clinical Trials as Topic; Diabetes Mellitus, Type 2/drug therapy; Humans; Hypoglycemic Agents/therapeutic use; Metabolic Syndrome X/etiology; Metformin/therapeutic use; Obesity/drug therapy; Piperidines/adverse effects/therapeutic use; Pyrazoles/adverse effects/therapeutic use; Receptor, Cannabinoid, CB1/antagonists & inhibitors/physiology; Risk Factors; Treatment Outcome

Abstract :

[en] Rimonabant, the first selective CB(1) receptor antagonist in clinical use, has been extensively investigated in the Rimonabant in Obesity (RIO) programme, comprising four 1-2 year placebo-controlled randomised clinical trials recruiting more than 6600 overweight/obese patients with or without co-morbidities. Rimonabant 20 mg daily consistently reduced body weight, waist circumference, triglycerides, blood pressure, insulin resistance and C-reactive protein levels, and increased HDL cholesterol concentrations in both non-diabetic and type-2 diabetic overweight/obese patients. Adiponectin levels were increased, an effect that correlated with HDL cholesterol augmentation, while small dense LDL cholesterol levels were decreased in patients receiving rimonabant 20 mg compared with those receiving placebo in RIO Lipids. Furthermore, in RIO Diabetes, a 0.7% reduction in glycated haemoglobin (HbA1c) levels was observed in metformin- or sulphonylurea-treated patients with type-2 diabetes, an effect recently confirmed in the 6-month SERENADE (Study Evaluating Rimonabant Efficacy in drug-NAive DiabEtic patients) trial in drug-naive diabetic patients. Almost half of metabolic changes occurred beyond weight loss, in agreement with direct peripheral effects. The positive effects observed after 1 year were maintained after 2 years. Rimonabant was generally well-tolerated, but with a slightly higher incidence of depressed mood disorders, anxiety, nausea and dizziness compared with placebo. In clinical practice, rimonabant has to be prescribed to the right patient, i.e. overweight/obese subjects with cardiometabolic risk factors and with no major depressive illness and/or ongoing antidepressive treatment, in order to both maximise efficacy and minimise safety issues. New trials are supposed to confirm the potential role of rimonabant in patients with abdominal adiposity, atherogenic dyslipidaemia and/or type-2 diabetes, i.e. at high cardiometabolic risk.

Disciplines :

Cardiovascular & respiratory systems
Endocrinology, metabolism & nutrition

Author, co-author :

Scheen, André ; Université de Liège - ULiège > Département des sciences cliniques > Diabétologie, nutrition et maladie métaboliques - Médecine interne générale

Language :

English

Title :

CB1 receptor blockade and its impact on cardiometabolic risk factors: overview of the RIO programme with rimonabant.

Publication date :

2008

Journal title :

Journal of Neuroendocrinology

ISSN :

0953-8194

eISSN :

1365-2826

Publisher :

Blackwell Publishing, Oxford, United Kingdom

Volume :

20 Suppl 1

Pages :

139-46

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 16 January 2009

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