In animal models, cannabinoid-1 receptor blockade produces a lean phenotype, with resistance to diet-induced obesity and associated dyslipidaemia.
Dr van Gaal and colleagues assessed the effect of rimonabant, a selective cannabinoid-1 receptor blocker, on bodyweight and cardiovascular risk factors in overweight or obese patients.
The team randomized 1507 patients with body-mass index 30 kg/m2 or greater, or body-mass index greater than 27 kg/m2 with treated or untreated dyslipidaemia, hypertension, or both, to receive double-blind treatment.
The patients were randomized to receive placebo, 5 mg rimonabant, or 20 mg rimonabant once daily in addition to a mild hypocaloric diet (600 kcal/day deficit).
The researchers considered the primary efficacy endpoint to be weight change from baseline after 1 year of treatment in the intention-to-treat population.
|Weight loss at 1 year was significantly greater with rimonabant versus placebo|
The research team found that weight loss at 1 year was significantly greater in patients treated with rimonabant 5 mg and 20 mg compared with placebo.
The investigators noted that significantly more patients treated with rimonabant 20 mg than placebo achieved weight loss of 5% or greater and 10% or greater.
Dr van Gaal concludes, “Rimonabant 20 mg produced significantly greater improvements than placebo in waist circumference, HDL-cholesterol, triglycerides, and insulin resistance, and prevalence of the metabolic syndrome.”
“The effects of rimonabant 5 mg were of less clinical significance.”
“Rimonabant was generally well tolerated with mild and transient side effects.”