Viagra For The Thighs?

By MICHAEL D. LEMONICK

No matter what she did, Cindy Smith just couldn't shed the 60 lbs. she'd gained during her pregnancy nine years ago. She went through over-the-counter weight-loss pills, liquid diets, starvation diets--always with the same result. "I would try it for about a week," says Smith, 38, a customer-service manager at a Houston bank. "I'd lose maybe 5 to 10 lbs., then get discouraged and end up dropping it."

A friend told her about an experimental diet drug being tested at nearby Baylor University, and Smith signed up. For two years, she and thousands of other overweight patients maintained a low-fat diet, exercised--and swallowed a medication called orlistat three times a day. "My clothes started fitting a lot looser after a month," she says. Today Smith is down to 150 lbs., her prepregnancy weight. Not only that, but she's maintaining the loss and hopes to drop even more.

Now millions of Americans will be getting the chance to see if orlistat works for them as well. The FDA ruled last week that the drug, made by Hoffman-LaRoche, can go on sale in the U.S. The dark blue capsules, under the trade name Xenical, could be available by prescription as early as this week.

Officially, orlistat is supposed to be taken only by the obese--those whose weight is at least 30% higher than it should be (27% for those with high blood pressure, high cholesterol or diabetes). But this is just a guideline: once a drug has been approved, doctors can prescribe it any way they want. And given Americans' obsession with getting slim, the demand could be enormous. "The reality," says Dr. Steven Heymsfield, deputy director of the Obesity Research Center at St. Luke's Roosevelt Hospital in New York City, "is that millions of people who have tried everything else and are frustrated with their weight will walk into their physician's office and say, 'I want Xenical.'"

In short, the FDA has unofficially launched a gigantic, uncontrolled experiment on the U.S. population, much as it did with the diet drug Redux in 1996 and the impotence pill Viagra in 1998. The Redux fad ended abruptly a year later when some users developed serious heart-valve defects--and major side effects are always a possibility with Xenical as well. With Redux, though, hints of danger had shown up in clinical testing. That's not true of orlistat, either in animals or in human studies conducted in some of the 17 countries where the medication is already available. (An initial suspicion that users had a higher incidence of breast cancer proved unfounded.)

One reason may be that hardly any of the drug is absorbed into the body. Unlike all previous diet drugs, orlistat doesn't reduce appetite. Instead, it interferes with an intestinal enzyme that breaks down dietary fat into an absorbable form. In essence, orlistat turns normal fat into something akin to Olestra, the fat-free fat Procter & Gamble has been using in snack foods since 1996.

As a result, about a third of the fat that would ordinarily be taken into the body is flushed right through the digestive system. Unfortunately, so are vitamins A, D, E and K, which bind to fat molecules. To make sure that patients don't develop vitamin deficiencies, the FDA requires that the Xenical label recommend that users take a multivitamin two hours before or after taking the drug.

The good news is that orlistat is flushed out of the body too: less than 1% of the drug remains in the system. Perhaps as a consequence, the only documented side effects--caused by excess fat coursing through the colon--are flatulence, greasy stools and, in a few cases, oily anal leakage.

That's one reason orlistat users are supposed to change their eating habits. If someone takes it without also switching to a low-fat diet, says Dr. Michael Hamilton, director of Duke University's Diet and Fitness Center, "that person is going to have a rude awakening."

Beyond that, orlistat isn't dramatically effective by itself. All the patients in the double-blind study went on strict eating regimens and exercise programs. Half of them were given orlistat, and half got an inert placebo. While those in the orlistat group lost an average of 10% of their initial weight after six months, the folks on the sugar pills lost nearly as much--a not inconsiderable 5%.

That's not enough of a difference to justify putting orlistat on the market, says Dr. Jules Hirsch, an obesity expert at Rockefeller University and a member of the FDA advisory panel that evaluated the drug. Hirsch voted against approval. "We're talking about something that will take a little bit of weight off--a little more than a placebo--for a few years," he says, "but that will not make obesity vanish. The question is, How valuable is that?"

By itself, not all that valuable. Ideally, says St. Luke's Heymsfield, doctors should first urge obese patients to change their diet and start exercising regularly. If they still can't lose weight, he would add orlistat to the mix. Another possibility, suggests Duke's Hamilton, is to use orlistat with an appetite suppressant. The value of this new drug, says Heymsfield, is that it adds to the available anti-obesity therapies and lets doctors tailor the treatment to a patient's needs. "I don't see Xenical as something to displace one or another of the currently available drugs," he says. "It's not a magic bullet. But having one more bullet, so to speak, is very helpful."

--Reported by Alice Park/New York

With reporting by Alice Park/New York