A new weight loss drug that works by blocking a cannabinoid receptor in the brain has had “modest” success at helping people both lose weight and keep it off, researchers say. It also seemed to improve other risk factors for cardiovascular disease beyond what would be expected from weight loss alone.
But critics say the study’s methodology may have been flawed, given that almost half of its participants dropped out.
Although 3045 people entered the study, the main results were based only on the 1602 who followed through to the end of the first year. “That may erroneously create a larger effect,” says Denise Simons-Morton, at the US National Heart, Lung and Blood Institute in Bethesda, Maryland, who co-wrote an accompanying editorial about the paper. She and her co-authors suggest the researchers should have made a greater effort to measure final outcomes in all their participants, even those who left early.
Xavier Pi-Sunyer, of St Luke’s-Roosevelt Hospital in New York, and his colleagues randomised their obese participants to take daily doses of either 5 milligrams or 20 mg of the drug, called rimonabant, or a placebo. The volunteers were also encouraged to stay on a weight-loss diet and given instruction on how to exercise more. Over the course of a year, various measures were taken, including weight, waist circumference, triglycerides (blood lipids), good cholesterol and blood pressure.
The researchers found that patients taking the larger dose were able to lose significantly more weight than those on placebo – an average loss of 6.1 kilograms versus 1.6 kg. Shedding even that amount of weight is clinically meaningful, says Pi-Sunyer. “It turns out it is quite helpful,” he says.
Notably, rimonabant seems to improve other measures beyond those expected from the level of weight loss achieved. Triglycerides, for instance, which increase a person’s risk of heart problems, dropped significantly and HDL, or good cholesterol, went up. While the mechanism is not known, Pi-Sunyer says they suspect an independent effect of the drug on lipid release.
The pill also appears to help in maintaining a new, lower weight. In the second part of the study, patients who had received active drug in the first year were then re-randomised for another year. Volunteers taking the 20mg dose in the second year were able to keep off the weight that they had lost; those taking the lower dose or the placebo put some weight back on.
The researchers suggest that sustained weight loss may require “continuous long-term treatment”. That may be good news for drug manufacturers, but a concern to people who may spend decades on a pill whose long-term effects are unknown.
“I worry about putting someone on a drug for a lifestyle and environmental problem,” says Simons-Morton. She points out that, in any case, lifestyle interventions have been shown to work better and last longer.
Journal reference: Journal of the American Medical Association (vol 295, p 761)