METHODS: Randomized controlled trials with
rimonabant were selected, through a Medline search, using the terms:
rimonabant,
endocannabinoid antagonist and
obesity. Reports of studies on large numbers of patients and covering the topics related to this review were included.
RESULTS AND DISCUSSION: In all the trials, there was a considerable reduction in
body weight in subjects taking 20 mg
rimonabant daily varying from 2.6 to 6.3 kg (placebo-subtracted changes).
Rimonabant was also associated with haemoglobin A(₁c) (HbA(₁c) ) reduction. In the
Rimonabant in
obesity (RIO)-diabetes study, diabetic patients taking
metformin or sulphonylureas showed decrease in HbA(₁c) levels by 0.5-0.6 ± 0.8% when
rimonabant was added, whereas in the
Serenade trial patients with untreated diabetes showed a reduction in HbA(₁c) of 0.8% vs. 0.3% with placebo. Similar results were obtained in diabetic patients under
insulin treatment. The lipidemic profile also improved in patients taking
rimonabant 20 mg daily; levels of
high density lipoprotein cholesterol (HDL-c) increased significantly while levels of
triglycerides (TRG) decreased in all trials, and positive effects were also observed in patients with atherogenic or untreated dyslipidaemia. In all the RIO studies, prevalence of the
metabolic syndrome decreased significantly. In addition, patients treated with 20 mg
rimonabant daily exhibited increase in
adiponectin. The metabolic changes observed were partly independent of the
weight loss and could be attributed to independent peripheral effect of
rimonabant. All these beneficial metabolic effects of
rimonabant could lead to progress in the prevention of
cardiovascular disease. However, in all the trials the incidence of adverse events leading to discontinuation was greater in the
rimonabant treated patients than placebo, mainly because of
psychiatric disorders (depression and anxiety),
nausea and
dizziness.
WHAT IS NEW AND CONCLUSION:
Rimonabant is effective in reducing weight in the obese but may lead to intolerable adverse effects most notably psychiatric effects, which make it unsuitable for routine use. However, the
drug provides useful proof of principle for this approach to
weight loss. Novel
cannabinoid type 1 receptor blockers with selectivity for peripheral receptors, may achieve similar metabolic results with decreased prevalence of psychiatric adverse effects.