Lingering Loss: In 2-year diet trial, new pill keeps off weight

An experimental diet drug looks like a long-distance success. New data indicate that obese adults who lose weight during a year of taking rimonabant and dieting keep the weight off during the following year, if they continue the regimen.

The drug, which Paris-based manufacturer Sanofi-Aventis calls Acomplia, blocks cells’ receptors for chemicals called cannabinoids, which include substances in marijuana. Some cravings for food and addictive substances depend on those receptors.

Yearlong trials of rimonabant had suggested that the drug aids initial weight loss. But the real test of an obesity treatment is whether weight shed in one year stays away the next.

So, endocrinologist F. Xavier Pi-Sunyer of Columbia University and his colleagues at 64 U.S. and 8 Canadian institutions enlisted more than 3,000 obese volunteers, mostly women, who agreed to take a daily pill while attempting to diet for 2 years. Throughout the study, investigators recorded the volunteers’ weight, blood concentrations of cholesterols, and other indicators of metabolic health.

During the first year, two-fifths of the volunteers took 20 milligrams per day of rimonabant, a similar number took 5 mg/day, and the rest took a placebo pill.

The higher dose of the drug produced the greatest benefit, including the most lost weight and the healthiest cholesterol concentrations, Pi-Sunyer reported Nov. 9 at a meeting of the American Heart Association in New Orleans.

Weight loss among volunteers who got rimonabant throughout the study “was fully maintained in year two,” says Pi-Sunyer. For example, 63 percent of volunteers getting 20 mg/day for 2 years weighed at least 5 percent less at the end of the study than they had at its outset. Only 37 and 33 percent of volunteers getting lower-dose rimonabant and placebo, respectively, achieved comparable weight loss.

In the study’s second year, half of each group that had been receiving rimonabant was unknowingly switched to placebos. Those whose pills were switched regained much of their lost weight. Pi-Sunyer says the sustained effect is attributable to rimonabant.

Regardless of which pills they were given, nearly half the volunteers dropped out of the study—a common problem in weight-loss trials—and were excluded from most statistical analyses. Side effects such as depression, anxiety, and nausea accounted for a small minority of dropouts in both the drug and placebo groups.

As for health-threatening side effects of the drug, “there don’t seem to be any red flags coming up over 2 years,” said Pi-Sunyer.

Other recent studies suggest that rimonabant might break addictions to nicotine, alcohol, and certain other drugs.

“This is the prototype of a new class of compounds,” endocrinologist Robert Eckel of the University of Colorado Health Sciences Center in Denver said at the heart meeting. “We should be encouraged that the drug appears safe at 2 years and effective” at maintaining weight loss. Nevertheless, he remains circumspect about the safety of the drug until there are data over longer periods and in groups with different characteristics.

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