Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia.
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.
Després
Jean-Pierre
JP
Quebec Heart Institute, Laval Hospital Research Center, and the Division of Kinesiology, Department of Social and Preventive Medicine, Laval University, Ste.-Foy, Que, Canada. jean-pierre.despres@crhl.ulaval.ca
Golay
Alain
A
Sjöström
Lars
L
D052242:Adiponectin / Q000097:blood; D000328:Adult; D000368:Aged; D019440:Anti-Obesity Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects; D063387:Cannabinoid Receptor Antagonists; D002784:Cholesterol / Q000097:blood; D004311:Double-Blind Method; D050171:Dyslipidemias / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D050177:Overweight; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000077285:Rimonabant; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood; D015431:Weight Loss / Q000187:drug effects
D052242:Adiponectin; D019440:Anti-Obesity Agents; D001786:Blood Glucose; D063387:Cannabinoid Receptor Antagonists; D007328:Insulin; D020738:Leptin; D010880:Piperidines; D011720:Pyrazoles; D014280:Triglycerides; D002784:Cholesterol; D000077285:Rimonabant