| Abstract |
BACKGROUND:
Rimonabant, a selective cannabinoid-1 receptor (CB1) blocker, has been
shown to reduce body weight and improve cardiovascular risk factors in
obese patients. The Rimonabant in Obesity-Lipids (RIO-Lipids) study examined
the effects of rimonabant on metabolic risk factors, including adiponectin
levels, in high-risk patients who are overweight or obese and have dyslipidemia.
METHODS: We randomly assigned 1036 overweight or obese patients (body-mass
index [the weight in kilograms divided by the square of the height in
meters], 27 to 40) with untreated dyslipidemia (triglyceride levels >1.69
to 7.90 mmol per liter, or a ratio of cholesterol to high-density lipoprotein
[HDL] cholesterol of >4.5 among women and >5 among men) to double-blinded
therapy with either placebo or rimonabant at a dose of 5 mg or 20 mg daily
for 12 months in addition to a hypocaloric diet.
RESULTS: The rates of completion of the study were 62.6 percent, 60.3
percent, and 63.9 percent in the placebo group, the group receiving 5
mg of rimonabant, and the group receiving 20 mg of rimonabant, respectively.
The most frequent adverse events resulting in discontinuation of the drug
were depression, anxiety, and nausea. As compared with placebo, rimonabant
at a dose of 20 mg was associated with a significant (P<0.001) mean
weight loss (repeated-measures method, -6.7+/-0.5 kg, and last-observation-carried-forward
analyses, -5.4+/-0.4 kg), reduction in waist circumference (repeated-measures
method, -5.8+/-0.5 cm, and last-observation-carried-forward analyses,
-4.7+/-0.5 cm), increase in HDL cholesterol (repeated-measures method,
+10.0+/-1.6 percent, and last-observation-carried-forward analyses, +8.1+/-1.5
percent), and reduction in triglycerides (repeated-measures method, -13.0+/-3.5
percent, and last-observation-carried-forward analyses, -12.4+/-3.2 percent).
Rimonabant at a dose of 20 mg also resulted in an increase in plasma adiponectin
levels (repeated-measures method, 57.7 percent, and last-observation-carried-forward
analyses, 46.2 percent; P<0.001), for a change that was partly independent
of weight loss alone.
CONCLUSIONS: Selective CB1-receptor blockade with rimonabant significantly
reduces body weight and waist circumference and improves the profile of
several metabolic risk factors in high-risk patients who are overweight
or obese and have an atherogenic dyslipidemia
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