If you take the diet drug Acomplia, you can keep off lost pounds only if you keep taking it, researchers say.

And those who stay on the drug keep their smaller waist, lower blood-fat levels, and higher good cholesterol levels.

If you don't cut your calories, Acomplia won't help you lose weight. But obese and overweight people who do eat less lost an average of 14 pounds if they were able to take Acomplia for one year. That's 10.5 pounds more than those who ate less and got an inactive placebo pill, reports F. Xavier Pi-Sunyer, MD, professor of medicine at Columbia University and chief of endocrinology at St. Luke's-Roosevelt Hospital, New York.

"I think it is exciting, because [Acomplia] has a new mechanism of action, and seems as effective [for weight loss] as any drug on the market," Pi-Sunyer tells WebMD. "[Acomplia] does a reasonable job of modest weight loss."

The results, first reported in 2004, appear in the Feb. 15 issue of The Journal of the American Medical Association.

The FDA has not yet approved Acomplia, but is expected to act soon. In clinical trials, the drug has helped people lose weight. Obese people seem to have an overactive cannabinoid system. By partially shutting this system down, Acomplia helps people resist the craving for highly palatable food popularly known as 'the munchies.'

Acomplia also helps people quit smoking.

The Catch: Quit Drug, Regain Weight

Pi-Sunyer and colleagues enrolled more than 3,000 obese and overweight adults in the U.S. and Canada. They were told to eat a calorie-restricted diet and to exercise. For a month, everyone got inactive placebo pills -- and, on average, everyone lost a few pounds.

Then a third of the people got low-dose (5 milligrams per day) Acomplia, a third got higher-dose (20 milligrams per day) Acomplia, and a third got placebo pills. A year later, half of those on Acomplia were switched to placebo pills for the second year of the study. Neither the participants nor the researchers knew which people got Acomplia and which got placebo until the pill codes were broken at the end of the study.

The bottom line:

· Those getting low-dose Acomplia lost more weight than those on placebo, but the difference was small.

· Those getting higher-dose Acomplia lost an average of 10.5 pounds more than those on placebo did.

· People who took higher-dose Acomplia didn't just lose weight, their waistlines shrank by an average of 2.4 inches; they had higher levels of good HDL cholesterol, and lower blood-fat levels. This is likely to lower risk of heart disease.

· In the second year, people on higher-dose Acomplia did not lose more weight -- but they kept off the weight they'd lost.

· People who stopped taking Acomplia gained back the weight they had lost.

These findings are based on people who stayed in the study -- not those who dropped out. People taking Acomplia were no more or less likely to drop out of the study than those on placebo. And Pi-Sunyer, a veteran of many weight loss studies, says these studies always lose about a half of their participants -- usually people who had hoped to lose more weight than they did.

Quitting Acomplia

By failing to include those who stopped taking the drug, the study gives a rosier-than-real-life picture of Acomplia benefits, says Denise G. Simons-Morton, MD, PhD, director of the clinical applications and prevention program at the National Heart, Lung, and Blood Institute.

"The real question is how useful Acomplia will be in a broad group of people, who may begin taking it and stop. It is not the whole picture, to look just at the people who keep taking it," Simons-Morton tells WebMD. "Until we have studies with a more rigorous design, we don't know yet how much of a benefit it would be for people trying to lose weight."

An editorial by Simons-Morton and colleagues accompanies the Pi-Sunyer report in JAMA. The editorial calculates that if one accepts Pi-Sunyer and colleagues' results, taking Acomplia helps people lose 4.5% of their body weight.

"That is the same weight loss you see with lifestyle changes," Simons-Morton says. "So why risk side effects when you can safely get the same effect by working on your diet and physical activity?

Acomplia Side Effects

The editorial notes that study participants taking Acomplia had a 2.7-fold increased risk of psychiatric disorders.

"The psychological effects are a concern, as we say in our editorial," Simons-Morton says. "With any new class of drugs there may be potential side effects you don't know about until substantial numbers of people are on them."

Pi-Sunyer agrees that the long-term safety of Acomplia can only be learned from post-approval studies. However, he says the drug was safe over the two years of the study.

"What I have seen in these two year data, it sounds like [Acomplia] is really quite safe," Pi-Sunyer says. "There is slightly greater incidence of depression, of anxious mood and irritability, and of nausea. But overall, there is a low level of adverse events. People seem to tolerate it quite well."

Pi-Sunyer notes that few people manage to lose weight and keep it off. By adding Acomplia to the ranks of existing weight loss drugs -- Meridia and Xenical -- patients will have yet another weight loss aid.

Simons-Morton questions the value of drugs that work only as long as one keeps taking them.

"If you take a drug, and when you get off it you gain your weight back, it is not better than going on a short-term diet," she says. "What people mean when they say 'I am going on a diet' is something temporary. Diets only work short term, just like the drugs. What works longer is a permanent change in eating and physical activity patterns. It is lifestyle choices, not going on a diet or taking a pill."

Pi-Sunyer notes, however, that many people simply won't lose weight without help.

"It is very difficult to maintain weight loss," he says. "A drug like this can be quite helpful in allowing an individual to maintain weight loss once it has been achieved. … If the FDA does approve it, it will be used quite heavily in the U.S. and around the world."

By Daniel J. DeNoon, reviewed by Louise Chang, MD

SOURCES: Pi-Sunyer, F.X. The Journal of the American Medical Association, Feb. 15, 2006; vol 295: pp 761-775. Simons-Morton, D.G. The Journal of the American Medical Association,Feb. 15, 2006; vol 295: pp 826-828. F. Xavier Pi-Sunyer, MD, professor of medicine, Columbia University; chief of endocrinology, St. Luke's-Roosevelt Hospital, New York. Denise G. Simons-Morton, MD, PhD, director, clinical applications and prevention program, National Heart, Lung, and Blood Institute, NIH, Bethesda, Md.