In a 2-year study of overweight or obese subjects, a marijuana derivative, or cannabinoid, called rimonabant (Acomplia) helped those who took it lose weight and improve their cardiovascular risk profile.

Weight loss occurred after 1 year of taking the drug and was sustained over a second year if treatment was continued. The agent also improved cardiometabolic risk factors even more than the amount of weight loss would have predicted.

“Our observations collectively suggest that rimonabant may well represent an innovative approach to the management of multiple cardiometabolic risk factors,” the authors write in the Journal of the American Medical Association.

Dr. F. Xavier Pi-Sunyer, from St. Luke’s-Roosevelt Hospital in New York, and his associates initially randomized 607 subjects to placebo, 1214 to rimonabant 5 mg, and 1219 to rimonabant 20 mg, while advising them to reduce their calorie intake by approximately 600 kcal/day and to increase physical activity.

Year 1 was completed by 51 percent to 55 percent of subjects, and outcomes were estimated based on an “intent-to-treat analysis.”

After 1 year, the proportion of subjects achieving at least a 5 percent weight loss was 48.6 percent of those treated with 20 mg, 26.1 percent for those treated with 5 mg, and 20.0 percent for those receiving placebo.

At the end of year 1, 602 in the 5 mg group and 660 in the 20 mg group were randomized to placebo or to continue treatment with rimonabant. Those who continued rimonabant 20 mg maintained a mean weight loss from baseline of 7.4 kg, while those assigned to placebo regained most of the weight they had lost.

Those treated with rimonabant for 1 year experienced increased levels of “good” HDL cholesterol and reduced insulin levels. Those in the 20-mg group also experienced reductions in triglycerides and in waist circumference, and did not show increased insulin resistance, as was observed in the placebo and 5 mg group.

“In patients receiving 20 mg of rimonabant, the observed effects at 1 year in levels of HDL cholesterol, triglycerides, fasting insulin, and in (insulin resistance) were approximately twice that attributable to the concurrent weight loss alone,” the authors point out. This suggests, they add, “a direct pharmacological effect of rimonabant on glucose and lipid metabolism.”

During year 2, among those on rimonabant 20 mg, HDL levels continued to increase and levels of triglycerides and the prevalence of the metabolic syndrome declined.

The authors note that patients taking rimonabant had more adverse events leading to study withdrawal, primarily due to psychiatric, nervous system, and gastrointestinal tract adverse events.

In a related editorial, Dr. Denise G. Simons-Morton and colleagues from the National Heart, Lung, and Blood Institute in Bethesda, Maryland, are critical of the study, noting that “analyses were required in which values were imputed for a substantial amount of missing data.”

This is likely to yield inaccurate results, they say, since most studies show that weight loss occurs early and that over time weight is usually regained, and this was not taken into account in the current study, making it subject to bias.

They further point out that meta-analyses of studies testing lifestyle interventions for weight loss found net weight reductions to be greater than those achieved in drug trials.

Therefore, the “current role (of drug treatments for obesity) should be limited pending further evidence,” Dr. Simons-Morton and her colleagues advise.

SOURCE: Journal of the American Medical Association, February 15, 2006.