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Conquer Fat
By Sheryl Gay Stolberg, March-April 2003
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The history of diet drugs, however, is littered with famous failures. The breakthrough was thought to come in 1994, with the discovery of leptin, a protein that obese mice lacked. Giving the protein to obese mice made them thin, and Amgen, a California biotechnology company, paid millions for the rights to develop a weight loss drug. But studies proved disappointing: Few people have leptin deficiencies, and giving leptin to most others did nothing to help them lose pounds.
Then came the fen-phen fiasco, which was blamed for several deaths in the 1990s. The Food and Drug Administration has since approved two new weight loss medications, Xenical and Meridia, but both cause side effects (such as diarrhea or high blood pressure) and neither is said to be very effective.
Today, the hottest research focuses on the natural hormone ghrelin, first identified by Japanese scientists in 1999. Ghrelin seems to increase appetite. Scientists at the University of Washington recently found that dieters who lose weight produce extra ghrelin—which could be why they become ravenous and regain every lost pound.
"Ghrelin could drive eating," Geliebter explains. Scientists are working feverishly to unravel how the hormone works, in the hopes of devising a pill that will safely curb hunger. But Schumacher and others don't believe there will be a single magic bullet. More likely, he says, within 10 or 15 years several drugs will be used in combination with one another, and with diet and exercise, to help people maintain a healthy weight.
In the short term, the most promising new medication for obesity is Axokine, tested in the 1990s as a treatment for ALS, or Lou Gehrig's disease. Although the drug, which is injected under the skin, did not help ALS patients, those who took it lost weight—a lot of weight—as a side effect. Its maker, Regeneron Pharmaceuticals, discovered that the drug works similarly to leptin and hopes it will work for the masses. A large study is underway, and the company plans to apply for FDA approval next year.
The drug Betsy Stewart is helping to test is promising, too. Schumacher couldn't identify it because of a confidentiality agreement, but it's clear that it's a so-called cannabinoid receptor antagonist made by Sanofi-Synthélabo, a Paris-based firm. Doctors (and most other people) know that smoking marijuana makes people hungry; the Sanofi drug antagonizes cannabis receptors to suppress appetite. "It's a novel approach,'' says Columbia University's Leibel, adding that the jury is still out on whether it will work.
Stewart, for one, is eager for the jury to be in. While fen-phen made her feel "buzzed," the white capsules don't make her feel unusual at all. Perhaps they are just a placebo, and diet and exercise are paying off. Or perhaps Stewart is one of the first Americans who's taking a truly effective weight loss medication and she's on the cutting edge of a new frontier in America's long-running battle with the bulge.
"If people could truly live with this," she says, "it could change everyone's life."
Sheryl Gay Stolberg is a reporter for The New York Times.
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