Get Ready for More Weight-Loss Drugs. But Will They Work?

The physiology of weight and need for safety may mean changing expectations of what drugs can do.

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Given the size of the obesity problem in the United States—and, increasingly, around the world—you'd expect the weight-loss drug market to be, well, huge. It's not. According to the market research firm Datamonitor, while the global market for drugs to combat diabetes will hit a projected $37 billion by 2018, the obesity drug market is likely to come to just $600 million. The reasons? A history of drugs haunted by sometimes dangerous side effects (including, most recently, the risk of heart problems associated with sibutramine, sold under the Meridia name in the United States, for some people with health issues) and the complex physiology of weight regulation.

Yet, ever cognizant of the market opportunities that would greet a safe, effective drug, manufacturers are teeing up new attempts. Two companies have filed for Food and Drug Administration approval for their medications, and another is expected to file this year. Other drugs are further back in the pipeline. And researchers are urging the exploration of new avenues that may lead to entirely different pharmaceutical approaches to making weight loss easier (although probably never easy).

Shouldn't the obese lose weight the old-fashioned way, through diet and exercise? In an ideal world, probably, but that approach hasn't been particularly successful over the years (see Do Program Diets Work? Rarely—Here are 7 Tips to Shed Pounds). But if willpower alone isn't the answer, neither is treating obesity as a chronic illness to be managed solely through medical means. Behavior and biology both contribute, says Madelyn Fernstrom, director of the nutrition and weight management program at the University of Pittsburgh Medical Center and author of The Real You Diet. Medications, she says, can help make healthful lifestyle choices a bit easier.

But there's not much ammo in currently available prescription options. Phentermine is an appetite suppressant approved by the FDA only for short-term use (up to 12 weeks). It's a stimulant—it was the "good" half of the infamous fen-phen combination that led to dangerous heart and lung damage—and has a powerful but short-lived effect, says Fernstrom. Another drug that muffles appetite, diethylpropion, is also potent but even shorter-acting. Sibutramine is a long-acting appetite suppressant that was initially studied as an antidepressant, but recent data suggest it may cause cardiovascular problems in people with uncontrolled high blood pressure or who have had previous heart attacks or strokes. (The FDA requested a stronger label warning; the European Medicines Agency recommended the drug not be used at all.) Finally, a drug called orlistat (sold over the counter as Alli and by prescription, in a higher dosage, as Xenical) acts not on appetite but by inhibiting a fat-digesting enzyme and causing some of the fat in meals to pass through the digestive tract without being absorbed. If a person eats too much fat, he or she can experience gas, diarrhea, and other unpleasantries. And those are the survivors among weight-loss products; fen-phen spectacularly crashed and burned, while the much-hyped rimonabant was never approved in the United States and faltered in Europe after reports of depression and suicidal thoughts in users. A host of other drugs were abandoned during early studies and never even submitted for approval.

[See Why You Should Think Twice Before Using Alli or Other Weight-Loss Aids.]

With all the drugs, weight loss tends to top out at about 4 to 6 percent of body weight, on average, and then plateaus. Stop taking the drug, and the weight usually comes back. It's not surprising that it's so tough to make the body give up pounds, says John Fernstrom, a professor of psychiatry and pharmacology at the University of Pittsburgh and director of research for the school's Weight Management Center. Fernstrom, who is Madelyn's husband, has researched weight-loss drugs. Like other physiological processes such as blood pressure, the balance of energy taken in from food and burned off through activity is fairly tightly regulated, he says. (Even if you gain 20 pounds over as many years, all it means is that your body isn't accounting for about 3,500 calories a year, or about 10 calories a day.) But things are lopsided; the body probably has a preference for fat accumulation, allowing weight to creep up far more easily than it creeps down, he says. Our bodies evolved in feast-or-famine conditions; when humans were hunter-gatherers, there was plenty of food available at some times of the year but not at others. So, he says, the pattern was to overeat during times of plenty, store fat, and then burning the fat when food wasn't readily available. Now, of course, conditions are different.