Obesity Drugs Work — Modestly

You probably don't need a scientific study to tell you there's no such thing as a magic weight-loss pill. But a paper published today on BMJ.com shows exactly that: Taking federally approved anti-obesity medications, such as Xenical and Acomplia, leads only to modest weight loss — an extra 6 lbs. to 10 lbs. (2.7 kg to 4.7 kg) a year — and it's not likely to radically trim down bulging waistlines. "People have to understand it's very difficult to lose weight," says lead author Raj Padwal, an assistant professor at the University of Alberta.

But that's not to say the drugs aren't successful. "There's a disconnect between what medical practitioners seek and what patients seek," says Padwal. Obese patients might go to their doctor looking to lose 100 pounds or more — they want to look the way they looked in high school. But doctors usually have more modest goals, tempered by their patients' experience — and by concerns about health over vanity. By a doctor's standard, even a 5% to 10% reduction in body weight can make a big difference to a patient's health. On that level, at least, there's little doubt anti-obesity medications can help. The BMJ (formerly the British Medical Journal) paper, a comprehensive review of 30 controlled trials on anti-obesity drugs, showed unambiguously that orlistat (Xenical), sibutramine (Meridia) and rimonabant (Acomplia) all resulted in weight loss — but the drugs' benefits extended beyond that. In one four-year trial, orlistat reduced the incidence of type 2 diabetes by almost a third; orlistat and rimonabant both cut patients' blood pressure; all three drugs lowered certain kinds of cholesterol. Not much data exists yet on the drugs' long-term effect on sickness and mortality, but further trials are underway.

Perhaps the drugs' biggest failure, says Padwal, is simply that patients don't take them as prescribed. The new study found that about 30% to 40% of participants in the 30 anti-obesity drug trials dropped out midway through — and these participants would have received consistent support from doctors. In the real world, Padwal estimates, the attrition rate is even worse: Less than 10% of his clinic patients, he says, are still taking the drugs three months after they're prescribed.

The reasons are many. A course of medication can be expensive — hundreds of dollars a year. Drugs also have side effects. Orlistat prompts weight loss by limiting the body's ability to absorb fat, but that can result in oily feces and sometimes incontinence. Sibutramine can raise blood pressure and lead to nausea and insomnia. Rimonabant is associated with an increased risk of psychiatric disorders like depression and anxiety. Still, Padwal says, "I think the main problem is the disappointment." For a lot of patients, the meager results of the medication don't justify their cost and unpleasantness.

The obesity epidemic, meanwhile, is swelling quickly. The World Health Organization estimates that a billion people worldwide are overweight, and 300 million are obese; more than a third of U.S. adults are now obese. So, why is it so hard to lose weight? "It looks very simple: People need to eat less and exercise more," Padwal says. "But if you drill down it's more complicated." Telling a single mother who works full-time that she should take a brisk walk in the inner city after work each day is not the most practical advice — she's unlikely to do it. And the stressed-out, sedentary American lifestyle — not to mention the overabundance of cheap, high-calorie foods — makes it difficult for people to eat as healthfully or exercise as much as they should.

For people who are very overweight or obese, Padwal says, virtually the only intervention that consistently gives impressive results is radical surgery, like gastric bypass. To curb the obesity epidemic, he says, patients need good old-fashioned commitment: They have to follow through with their weight-loss plan long-term, monitoring and adjusting it year after year. But, for now, he still prescribes anti-obesity drugs.