The blockade of the endocannabinoid CB1 receptors and its influemce on cardiometabolic risk: lessons from Rimonabant In Obesity (RIO) trials

The impact of visceral obesity epidemic on the incidence of diabetes mellitus andcardiovascular disease is a major concern in the public health management. Even if lifestylemodifications still remain the cornerstone of obesity treatment, the pharmacological approach couldhelp not only to reduce body weight and visceral fat but also their metabolic and cardiovascularcomplications. It has been shown that endogenous cannabinoid system is overactivated in obese miceand both in subcutaneous and visceral adipose tissue of obese patients. The CB1 antagonist rimonabantis able to antagonize most of the behavioural and metabolic effect of endocannabinoid overactivation. Four double-blind trials compared rimonabant 5 mg or 20 mg daily with placebo in more than 6600 individuals. RIO-Europe, RIO-Lipids, RIO-North America, and RIO-Diabetes have published 1 yearresults. RIO-North America also included a second year of follow-up. These trials showed that inpatients with obesity, including those with cardiovascular risk factors, continued therapy withrimonabant as compared with placebo is associated with a significant reduction in body weight andwaist circumference. Such therapy is also associated with other favorable changes in thecardiometabolic risk profile, including an improvement in the lipid profile and in glycaemic controlin type 2 diabetic