Rimonabant is the first of a new class of selective
cannabinoid receptor-1 blockers. It reduces the overactivity of the
endocannabinoid system, improving
lipid and
glucose metabolism and regulating food intake and energy balance. In four randomised, double-blind clinical trials in
overweight or obese adults with or without
type 2 diabetes and/or dyslipidaemia, oral
rimonabant 20mg once daily reduced weight and waist circumference to a significantly greater extent than placebo. A significantly greater proportion of
rimonabant than placebo recipients achieved the clinically significant
weight-loss target of > or =5% or > or =10% of initial weight.
Rimonabant was associated with significant improvements in glycaemic control relative to placebo, with approximately equal to 57% of the reduction in glycosylated haemoglobin being independent of the effects of
weight loss in one trial. Improvements in other cardiometabolic risk factors (i.e. increases in
high-density lipoprotein-cholesterol [HDL-C] and decreases in
triglyceride [TG] levels) were significantly greater with
rimonabant than with placebo. The improvement in
lipid profile also demonstrated a weight-independent effect, with approximately equal to 47-58% of the improvement in HDL-C and TG being beyond that expected through
weight loss alone.
Rimonabant was generally well tolerated, with most adverse events considered mild to moderate in severity.