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Rimonabant in Obesity - RIO-Lipids
Description:
The goal of the trial was to evaluate the efficacy and safety of rimonabant, the first selective cannabinoid type 1 (CB1) receptor antagonist, compared with placebo for weight reduction.
Hypothesis:
Treatment with the selective CB1 receptor antagonist rimonabant will be associated with larger weight reduction compared with placebo in patients with abdominal obesity and abnormal lipid profiles.
Study Design
Study Design:
Patients Enrolled: 1,036
Mean Follow Up: One year
Patient Populations:
Overweight or obese patients, defined as BMI 27-40 kg/m2), and untreated dyslipidemia, defined as triglyceride levels >1.69 to 7.90 mmol/L, or a ratio of total cholesterol to HDL of >4.5 in women and >5 in men.
Exclusions:
Morbidly obese patients (BMI >40 kg/m2)
Primary Endpoints:
Change in weight from baseline at the last observation carried forward
Drug/Procedures Used:
Patients were randomized to a fixed daily dose of rimonabant 5 mg (n=345), rimonabant 20 mg (n=346), or placebo (n=342) treatment for one year.
Principal Findings:
Mean baseline body mass index (BMI) was 34 kg/m2, and mean weight was 96 kg. Weight loss was greater in the high-dose rimonabant arm (20 lbs) than placebo (p<0.001), as was waist circumference (3.4 inches).
Frequency of weight loss ≥5% of body weight was 30.0% in the 5 mg arm and 58.4% in the 20 mg arm, higher than the placebo arm (19.5%, p<0.001 vs. high dose). When restricted to patients who completed the full one year of treatment, the rates were even higher (72.9% for high dose, 41.8% for low dose, and 27.6% for placebo, p<0.001 vs. high dose). Similar results were observed when using a threshold of weight loss ≥10% of body weight (32.6% for high dose, 10.6% for low dose, and 7.2% for placebo, p<0.001 vs. high dose).
Patients in the rimonabant 20 mg arm had a 23% high-density lipoprotein (HDL) increase (p<0.001), a 15% decrease in triglycerides (p<0.001), but no significant difference in low-density lipoprotein level. C-reactive protein reduction was greater in the rimonabant 20 mg arm compared with placebo (0.9 mg/L reduction in high dose vs 0.4 mg/L in placebo, p=0.02). Adiponectin level reduction was greater in the rimonabant 20 mg arm compared with placebo (41% increase in high dose, from 5.8 to 8.2 vs. 14% increase in placebo, from 5.9 to 6.7, p=0.001).
The most frequent adverse event in the rimonabant group was nausea. There was no difference in treatment discontinuation between groups (36.1% for high dose, 39.7% for low dose, and 37.4% for placebo).
Interpretation:
Among patients with abdominal obesity and abnormal lipid profiles, use of the selective CB1 receptor antagonist rimonabant in a 5 mg or 20 mg dose was associated with greater weight reduction after one year of treatment compared with placebo, with a numerically larger reduction in the 20 mg group. Additional benefits were observed in HDL and triglyceride levels with rimonabant.
Obesity is a growing epidemic, which has been shown to contribute to a variety of co-morbidities, including increased coronary heart disease, diabetes, and hyperlipidemia. Few pharmacologic agents have been identified as both safe and effective in reducing weight, pointing to the potential importance of the present study. Further evaluation is warranted.
References:
Després JP, et al. Effects of Rimonabant on Metabolic Risk Factors in Overweight Patients with Dyslipidemia. N Engl J Med 2005;353:2121-34.
Presented by Dr. Jean-Pierre Despres at the American College of Cardiology Annual Scientific Session, March 2004.
Keywords: Obesity, Abdominal, Nausea, Hyperlipidemias, Weight Loss, Body Weight, Coronary Disease, Pyrazoles, Lipoproteins, LDL, Waist Circumference, C-Reactive Protein, Piperidines, Body Mass Index, Cannabinoid Receptor Antagonists, Adiponectin, Receptor, Cannabinoid, CB1, Lipoproteins, HDL, Triglycerides, Diabetes Mellitus
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