SUSAN DENTZER: Lorraine M. is in her mid-30's, and full of vigor. But she also has a serious health problem: At 5'7" and 190 pounds, she's obese, about 35 pounds overweight.
LORRAINE M.: Five years ago I got married and settled down, you know, I could say, and I just started gaining weight.
SUSAN DENTZER: These days, when M. goes out to eat with her friends, she tries to eat lighter foods. That's after years of struggling in vain to lose weight. Recently, her family physician raised a red flag.
LORRAINE M.: And he said that my cholesterol was high, and it's something that I could totally fix with just diet and - you know -- weight loss. And I said, you know, "wow, I can't believe that my cholesterol's high. I never thought that I would be in this situation." So I made an appointment to see Dr. Aronne.
SUSAN DENTZER: That's Dr. Louis Aronne, an obesity specialist at Cornell University's Weill Medical College in New York.
DR. LOUIS ARONNE: Obesity is a health risk because it's the major cause of diabetes; it's one of the major causes of high blood pressure and high cholesterol. And when you add those up, it's one of the major risk factors for coronary artery disease, the leading killer in the United States.
SUSAN DENTZER: Obesity also afflicts a quarter of a billion people worldwide, and roughly one out of five U.S. adults. To combat Lorraine M. 's obesity, Dr. Aronne recommended a low-fat diet and plenty of exercise. But he also prescribed a controversial drug that has just come on the market in the United States: Xenical.
DR. LOUIS ARONNE: Xenical is a medication that works like no other medication for control of weight.
SUSAN DENTZER: Also known as Orlistat, Xenical prevents some dietary fat from being absorbed by the body. Manufactured by the international pharmaceutical company Roche, it's been available in much of the world for several years. Recently, it was approved by the Federal Food and Drug Administration for use in the United States, to the relief of millions like Lorraine M. .
A human resources administrator for Bloomingdale's in New York, M. is considered obese by virtue of a measurement known as her Body Mass Index, or BMI. That's a formula computed by comparing the metric equivalent of a person's weight to his or her height. A person is obese with a BMI of 30 or higher. Roughly speaking, that translates into a six-foot tall man weighing at least 220 pounds, or a 5'6" woman weighing 185 pounds. M. 's BMI is right at 30. A half hour before she started that lunch with friends, M. popped a Xenical pill into her mouth, as she now does before every meal. Each pill costs about $1.50, and isn't covered by her health insurance. When we interviewed M. after ten days on the medication, she had already lost about six pounds.
SUSAN DENTZER: What's your goal? How much weight do you want to lose?
LORRAINE M.: I'd like to lose 40 pounds.
SUSAN DENTZER: If she maintains the pace, she could reach her goal in several months, and Dr. Aronne thinks her chances of success are good.
DR. LOUIS ARONNE: Medication helps people who are trying to lose weight, but can't stick with the plan, to stick with it a little bit better. So that if you look at the patients who we've seen who've lost 20, 30, or 40 pounds taking Xenical, they're very, very happy, and they're getting a lot of benefit.
SUSAN DENTZER: That enthusiasm stands to make Xenical the next blockbuster entry in the battle against excess weight. It's a field that has become crowded in recent years with medications like Meridia, an appetite suppressant manufactured by Knoll Pharmaceuticals. Like other commonly used weight- loss medications, Meridia manipulates brain chemistry to curb the desire to eat. But Xenical's approach is different. Once ingested, it lodges in the digestive tract. There, it binds to an enzyme produced by the pancreas that is instrumental in digesting fat.
DR. LOUIS ARONNE: One-third, about 30 percent of the fat that's consumed is not digested, and passes through the gut. 70 percent of the fat that's consumed is appropriately digested and absorbed into the body.
SUSAN DENTZER: There's one problem: If people consume a lot of fat in their diet while taking the drug, they can experience some unpleasant side effects. Joann Chase, a New Jersey political consultant, is another of Dr. Aronne's patients.
JOANN CHASE: In an hour, I'll have a stomach ache if I eat an éclair. So you just don't eat the éclair-- at least, I haven't. I mean, it's not dinner table conversation. You know, there is a cause and then there is an effect.
SUSAN DENTZER: An effect that can include bloating, flatulence, oily stools, and an urgency to get to the bathroom. What's more, Xenical can also prompt the body to flush out fat-soluble vitamins like A, D, E, and K. That's why patients are advised to take multivitamin supplements with each dose of the drug.
DR. JULES HIRSCHA, Rockefeller University: There's the worry that they may not take the supplement, and we don't know what the long-term effects of that would be.
SUSAN DENTZER: Dr. Jules Hirsch is an obesity expert at New York's Rockefeller University who frequently collaborates with Dr. Aronne on research. He served on an FDA advisory panel that split 50/50 on whether the drug should be approved. Hirsch voted no, because he believed the drug's minuses outweighed the plusses.
DR. JULES HIRSCH: In all of these instances when we examine a drug, we're very interested in the risk- benefit ratio, and it seemed to me that the benefits of taking Xenical were quite small.
SUSAN DENTZER: Hirsch points to clinical studies of Xenical that raised questions about how much the drug really helped people lose weight. In those trials, one group of patients was given Xenical and put on a reduced-calorie diet. Another group got the new diet and a placebo. After a year, the group on Xenical had lost 10 percent of body weight, just four percentage points better than the group on placebo. In other words, a 200-pound man would only have lost eight more pounds on Xenical than with the low-calorie diet alone.
DR. JULES HIRSCH: The contention is that, well, some of the people in the Xenical group lost more. That's right. But some of the people in the placebo group also lost more. So I just don't think one can make a great case for Xenical on the basis of the occasional person who responds to it.
SUSAN DENTZER: But Dr. Aronne argues that looking at just the average results from the trials obscures the fact that some patients lose lots of weight on the drug. Meanwhile, those who lose only a few pounds still derive health benefits.
DR. LOUIS ARONNE: Why is that? Because the first weight that you lose is intra-abdominal, or visceral fat. That's the worst fat in your body for your health, and what it does is cause much of the metabolic damage that's associated with obesity.
SUSAN DENTZER: Still, even Aronne is concerned about other developing trends. In an age of global commerce, the drug is readily available over the Internet, and can even be obtained from abroad without a prescription. Joann Chase learned that after she got a prescription from Dr. Aronne, but couldn't find the drug locally.
JOANN CHASE: So I went home and got on the Internet, and I typed in "Xenical." And up came about 50 or 60 places written in Chinese, German, French, every language you can imagine, to purchase Xenical, no prescription, no nothing. And I gave them my credit card, and it actually came from New Zealand in two days.
SUSAN DENTZER: That raises concerns that thousands of people may be obtaining Xenical outside a doctor's care. They may also be using it even if they aren't obese, and don't fall within FDA guidelines for the drug.
DR. JULES HIRSCH: The hazards of using this are greatly multiplied if there is no physician surveillance of what is going on.
SUSAN DENTZER: Yet another worry is that some doctors have already begun prescribing Xenical in combination with other drugs, such as the appetite suppressant Phentermine. But this so-called Xen-Phen combination hasn't been studied to determine its safety or effectiveness. That fact invokes grim memories of an earlier drug combination known as Fen-Phen, or Fenfluramine and Phentermine. The combination was once widely prescribed for weight loss. But in 1997, Fenfluramine and a similar drug, Dexfenfluramine, were linked to heart valve disease, and were subsequently withdrawn from the market.
DR. LOUIS ARONNE: I think that just using drugs in combination, without looking at it at all, is not an appropriate thing to do in treating any disease.
SUSAN DENTZER: Lorraine M. agrees.
LORRAINE M.: I do have some fear of risk, so I just am taking the Xenical because it seems to be working for me.
SUSAN DENTZER: But she's also under no illusions about the difficult road ahead.
LORRAINE M.: I don't think there's any magic pill about weight loss. I think you need to put effort into it, and the Xenical is just actually helping along.
SUSAN DENTZER: According to pharmaceutical industry analysts, Roche's global sales of Xenical could soar beyond $2 billion annually within several years.