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Simple Pill Not a Simple Answer to Obesity

Insights about rimonabant from the RIO-North America trial

Rimonabant, a selective cannabinoid-1 receptor blocker, showed promise in reducing body weight and improving lipid profiles of obese adults in the manufacturer-funded RIO-LIPIDS and RIO-Europe trials. Now we have data from RIO-North America, in which 3045 obese people (mean age, 45; 80% women; mean BMI, 38) were randomized to receive 5-mg rimonabant (1216 participants), 20-mg rimonabant (1222), or placebo (607) daily for 1 year. All groups were assigned to a mildly hypocaloric diet (deficit, 600 kcal/day).

The 299 placebo recipients who completed their assigned regimens at 1 year received placebo for a second year. The rimonabant recipients who completed their assigned treatments (602 on 5 mg, 660 on 20 mg) were re-randomized to receive, for the second year, either the same rimonabant dose they had been taking or placebo.

In analyses at 1 year — which did not include nonadherent participants (about 40% of the cohort) or dropouts (7%) — rimonabant showed significant advantages over placebo, particularly at the 20-mg dose. This dose was associated with 5 kg more weight loss, on average, than was placebo, plus significantly greater improvements in waist circumference, triglyceride levels, and HDL-cholesterol levels. Benefits were largely maintained at 2 years by participants who remained on 20-mg rimonabant but not by those switched to placebo, whose results at 2 years were similar to those of the permanent placebo recipients. Side effects were similar among the groups, but they led to study withdrawal by more rimonabant recipients than placebo recipients during the first year.

Comment: Among study completers (just over half of initial enrollees), 20-mg rimonabant was associated with significant improvements in body weight and metabolic parameters. However, given the high nonadherence rate and lack of an intention-to-treat analysis, we must interpret the data cautiously. In short, rimonabant’s benefits might have been overestimated because nonadherence is often associated with regaining weight. A pill has appeal as a weight-loss aid for some patients, but long-term, comprehensive lifestyle changes — a reduced-calorie, low-fat diet and increased physical activity — are crucial for combating obesity in individuals and population-wide.

— JoAnne M. Foody, MD

Published in Journal Watch Cardiology March 30, 2006

Citation(s):

Pi-Sunyer FX et al. for the RIO-North America Study Group. Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients. RIO-North America: A randomized controlled trial. JAMA 2006 Feb 15; 295:761-75.

• Original article (Subscription may be required)
• Medline abstract (Free)

Simons-Morton DG et al. Obesity research — Limitations of methods, measurements, and medications. JAMA 2006 Feb 15; 295:826-8.

• Original article (Subscription may be required)
• Medline abstract (Free)