Some concerned new Alli in weight-loss has unpleasant side-effects

How badly do you want to be skinny? Is it worth soiling your underwear?

Those questions will likely confront users of the new Alli, the first over-the-counter diet drug approved by the U.S. Food and Drug Administration.

Alli (pronounced al-EYE) went on sale for the first time about a week ago - a stronger prescription form, Xenical, has been available since 1999 - and its promotional material alone makes for strong medicine: The drug, which helps people lose small amounts of weight, can cause oily discharges, uncontrolled bowel movements, and gas if you eat too much fat.

Its marketing effort makes an impression by telling users to wear dark pants and carry extra clothes in case they soil themselves.

"Well, that sounds attractive, doesn't it?" Jay Leno cracked Monday on "The Tonight Show." "You lost a couple of pounds, and you're on a date with that special girl. `Excuse me while I change my pants.'"

NBC's Conan O'Brien also spoke up to pooh-pooh Alli, suggesting that "the drug comes in three forms: pills, capsules and chimichangas."

Even the serious Boston-based Prescription Access Litigation Project, which often sues drug companies, got gleeful. It gave the drug's maker, GlaxoSmithKline P.L.C., its `With Allies Like This, Who Needs Enemas?' Award for Irresponsibly Selling a Formerly Prescription-Only Weight Loss Drug Over-the-Counter.

The drug's backers say that the embarrassment is exaggerated and that the effects can be managed by a low-fat diet.

Only half of all users had "fecal urgency" or related effects in clinical trials, and just 5 percent quit for those reasons, said Vidhu Bansal, director of medical affairs for GlaxoSmithKline's consumer health division.

"They actually served as a positive feedback tool," she said. "It reminded them that they cheated on their diet."

Caroline Apovian, a Boston physician who wrote "The Alli Diet Plan," which shows how to minimize problems by eating low-fat foods, said she did not understand the shame people might feel over losing bowel control. "It's also embarrassing to be obese," said Apovian, who was a paid consultant to GlaxoSmithKline in getting Alli approved for over-the-counter sales. "It's embarrassing to be dead."

GlaxoSmithKline executives are pitching Alli as part of a lifestyle change, which includes a commitment to eat better and exercise more. Users can log in their progress on the drug's Web site - - and interact with other customers or ask questions of a pharmacist, a nutritionist, a chef, and a fitness specialist.

The firm, with a U.S. headquarters in Philadelphia, paid $100 million to Xenical's maker, Roche, for the rights to sell Alli over the counter. GlaxoSmithKline is spending an additional $150 million in a marketing campaign that includes a 60-second television ad and print ads appearing this month in most major magazines, read by 33 million people.

Bill Trombetta, professor of pharmaceutical marketing at St. Joseph's University in Philadelphia, said the comedians' attention has an initial upside. "They got your attention. This is on everyone's lips," he said. "You can't buy this kind of publicity."

But will the exposure move people to try it?

Maybe at first, said Kelly Brownell, who directs the Yale Center for Eating and Weight Disorders. But he predicts "sales will tail off fairly quickly."

"The people who will try it won't lose much weight and won't provide very good word-of-mouth," he said.

"Both the benefits and the side effects are overstated," Brownell added. "It's not going to hurt many people, and it's not going to help many people."

Marion Nestle, a nutrition professor at New York University and a frequent critic of the food industry, noted that many users may replace fat calories by eating more carbohydrates. "A lot of Alli takers will do that and wonder why they aren't losing weight," she wrote in an e-mail.

The early results are sketchy.

In the California beach town of Santa Monica, a Los Angeles Times reporter found that Alli bottles were flying off store shelves.

But in Philadelphia, once dubbed the nation's fattest city, Alli's arrival appeared to be less of a sensation.

"We do have it in stock. No one has inquired about it," pharmacist Maria Taylor at Narberth Pharmacy, said last week, echoing several other Philadelphia-area pharmacists. "Maybe it should come with a coupon for Depends," the adult diaper.

Alli contains 60 milligrams of orlistat - half the amount found in prescription Xenical. The over-the-counter version is taken three times a day with meals and costs from $60 to $67 for a month's supply. A year's worth costs at least $720.

The prescription drug's U.S. sales have been fading, from $135 million in 2002 to $93 million last year.

Despite the fact that obesity rates are surging, an effective drug remains elusive. "Eating is so fundamental for human existence that the body has multiple redundant systems," said Gary D. Foster, who directs Temple University's Center for Obesity Research and Education and was a consultant to GlaxoSmithKline for its Alli Web site. "So if you block one pathway, it's evolutionarily smart to have a backup."

Alli works by blocking the digestive enzyme Lipase, which aids in fat absorption. The firm estimates that Alli blocks about 25 percent of the fat that reaches the gut.

But too much fat can cause oily discharges. "You may recognize it as something that looks like the oil on top of a pizza," an Alli brochure says cheerily.

That is what happened to Paula Miguel, 35, of Hopatcong, N.J. She was one of 400 people picked by the drug firm to receive a six-month supply of Alli for free.

She said it was hardest the first week to establish her routine to walk more and eat better.

She felt a strong urge to go after downing some greasy crab cakes at a friend's house. "When I went to the bathroom, it was orangey, like an oil," she said.

But, she said, that happened only once since she began April 18. Overall, she said, she has lost 23 pounds, falling to 170 pounds on her 5-foot-3 frame. "It's not as bad as they say," said Miguel. "I eat better ... I'm more active. For me, it works fine."

The company said users could expect to lose an average of 10 pounds in a year. But that's high, independent experts say. The more potent prescription version helped participants lose an average of 6.3 pounds by the end of a year, according to researchers who analyzed 50 studies for a 2005 article in the Annals of Internal Medicine.

Paul Woolf, chairman of the department of medicine at Crozer-Chester Medical Center in Chester, Pa., was on the FDA advisory committee that in 2006 recommended that Alli be freed from prescription status.

He called Alli "a real niche product" that causes modest weight loss.

"No one is going to abuse it," he said. "They're going to be very unhappy if they do."