Millions take popular drugs to lose weight, but the long-term risks and benefits of these medications aren't known, two Canadian researchers contend.

Drs. Raj Padwal and Sumit Majumdar, of the University of Alberta, said long-term studies are needed to determine whether losing weight on drugs such as sibutramine (Meridia), orlistat (Xenical) and rimonabant (Acomplia) actually reduces the risks of heart attack, stroke and diabetes associated with being overweight or obese.

The physicians expressed their views in the Jan. 6 issue of The Lancet.

"These three medications will likely lower weight, modestly, but we need better studies," Padwal said. "The studies that are out there don't provide information on cardiovascular disease and cardiovascular deaths. The other problem is that they are not long-term and have high dropout rates. We really need to know what the net benefits of these medications are, and truly know whether we should be using them or not."

Padwal and Majumdar reviewed all the published studies on the risks and benefits of the drugs.

For example, Meridia is associated with improvement in some cardiovascular risk factors, but for some patients it raises blood pressure, Padwal said.

"If you are going to prescribe a weight-loss drug, the ultimate goal is not a cosmetic one. The ultimate goal is to get that person to be healthier and lower their risk of having cardiovascular problems," Padwal said. "If you are going to give a medication that raises the blood pressure, then you have to question, is the net benefit advantageous or am I putting this patient at increased risk."

Padwal noted that studies are now under way to determine the long-term benefits and risks of these drugs. But such studies take time, and drugs such as Merida and Xenical have been on the market for several years. "That's going to be eight to nine years of using the medication before we finally get more definitive evidence whether they are beneficial or not," he said.

The ultimate question, Padwal said, is whether the modest weight loss associated with these drugs is really a benefit for overall health. People who exercise may only lose a little weight but they can significantly reduce their risk of heart attack and stroke and diabetes, he noted.

"Until you have a study that shows that these medications lower the incidence of heart attack, the incidence of stroke, cardiovascular mortality, overall mortality, you don't know what the overall net benefit of these medications are," Padwal said.

One expert doesn't think drugs are the solution to the obesity epidemic gripping the United States and many other developed nations.

"To date, the history of weight-loss drugs is not very encouraging," said Dr. David L. Katz, an associate professor of public health and director of the Prevention Research Center at Yale University School of Medicine. "The two FDA-approved weight-loss drugs now available, sibutramine and orlistat, have serious potential side effects, limited efficacy, and work only as long as they are taken."

Rimonabant, a new drug soon to be available, blocks a receptor influencing appetite, and looks promising. But studies suggest its effects may wear off over time, and side effects are unknown, Katz said.

"Obesity is less about the body doing anything wrong than it is about an environment that is all wrong for our bodies," he said. "We are adapted to survive in a world where calories are scarce and physical activity demands high. To use pharmacotherapy to fight obesity, we are, in essence, hoping to redirect the fundamental activities of human metabolism. I don't think we'll ever succeed in doing so, without dire cost in toxicity and side effects."