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

The impact of visceral obesity epidemic on the incidence of diabetes mellitus and cardiovascular disease is a major concern in the public health management. Even if lifestyle modifications still remain the cornerstone of obesity treatment, the pharmacological approach could help not only to reduce body weight and visceral fat but also their metabolic and cardiovascular complications. It has been shown that endogenous cannabinoid system is overactivated in obese mice and both in subcutaneous and visceral adipose tissue of obese patients. The CB1 antagonist rimonabant is 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 year results. RIO-North America also included a second year of follow-up. These trials showed that in patients with obesity, including those with cardiovascular risk factors, continued therapy with rimonabant as compared with placebo is associated with a significant reduction in body weight and waist circumference. Such therapy is also associated with other favorable changes in the cardiometabolic risk profile, including an improvement in the lipid profile and in glycaemic control in type 2 diabetics.