The Diet Pill Dilemma

Karen Paris knew she was eating too much when she caught herself eating off her daughter's plate. "I had gotten into some really bad habits, and my portions were huge," she recalled.

So she began a campaign to lose 25 pounds. There was no secret shortcut: She joined Weight Watchers, cut back on portions at every meal and took up aerobics and circuit training at the YMCA near her Catonsville home.


Her weight has since fluctuated, but Paris, now 44 and paid to run weekly sessions for Weight Watchers members, has managed to keep it within 5 pounds of the goal she achieved back in 1995.

"I've been doing this for 12 years, and it's still a struggle," she said.


For those who set weight-loss goals like Paris, a little help may finally be on the way. This month, the Food and Drug Administration gave GlaxoSmithKline the green light to sell Orlistat without a prescription - making it the first over-the-counter diet drug on the market. It's expected to be available as early as this summer.

And that raises a question: In a country where almost a third of the adult population is obese - an estimated 60 million people - why is it so difficult to come up with a diet drug?

The answer lies partly in the troubled history of weight-loss medication and partly in our genetic makeup, experts say.

"Either they didn't work well, or if they worked, it was a double-edged sword and there were significant health risks involved," said Dr. Sidney M. Wolfe, director of Public Citizen's Health Research Group, a Washington-based organization frequently critical of the FDA.

Eating may seem like a matter of choice to us, but it's controlled by a brain that evolved when we were hunter-gatherers and food intake was a matter of survival, said Dr. Arthur Frank, medical director of the George Washington University Weight Management Program.

Frank, who has worked as an adviser to Glaxo, said overcoming these hard-wired mechanisms is difficult with a pill.

"Eating is an intensively regulated and highly controlled activity," he said. "There's no other biological control mechanism as complicated. It's closely related to survival."

After you lose weight with a diet pill, your brain will begin to detect the loss and compensate by increasing your drive to eat, Frank said. For many people, the brain's signaling system is out of balance when it comes to food intake, so that just telling an obese person to eat less doesn't work.


"It's like saying to someone who's depressed, all you have to do is pull yourself together, or saying to someone with asthma, just breathe deeply," Frank said. "There's more to it than that."

Our metabolism also slows down when we diet, just as it does as we age, experts say. That's why someone who normally burns about 2,000 calories a day will burn only 1,800 once they begin dieting, said Ray Hinish, a pharmacist, personal trainer and partner in Your Prescription for Health, an Owings Mills outlet for medications and health supplements.

Not surprisingly, most experts agree that weight loss isn't a matter of finding the right pill, but changing lifestyles.

"Weight gain isn't an artifact of any drug deficiency. It's an artifact of our poor eating habits and our poor exercise habits, and you can't put that in a bottle," Hinish said.

Judith Ryan, who with Paris' help lost 170 pounds over 3 1/2 years, agrees. "One of the problems is as Americans we're still looking for the magic pill," she said. "What worries me is that people who take the pill aren't going to diet and exercise, and I think a lot of people are going to be disappointed."

Diet pills also have "always been a troublesome category of drugs," said Frank Palumbo, director of the Center on Drugs and Public Policy at the University of Maryland School of Pharmacy.


There are three ways that diet drugs have traditionally worked: by suppressing hunger, providing a sense of being full or speeding up our metabolism rate so that we burn more calories, Frank said.

But the diet drug industry has had a history of problems. The combination known as fen-phen was recalled in 1997 because of heart valve problems that led to litigation - and eventually cost its manufacturer, Wyeth-Ayerst Laboratories, billions of dollars in damages.

In 2004, the FDA banned all diet supplements with Ephedra - a stimulant that increases metabolism - because it was linked to a number of deaths. Meridia, another prescription diet drug approved for long-term use in the United States, was the focus of a recent FDA review because of links to high blood pressure and stroke.

"The history of these diet drugs, both on the prescription side and the over-the-counter side, is that there are horrendous health hazards," said Wolfe, who requested the FDA review of Meridia.

Glaxo plans to market Orlistat under the name Alli. The drug, which works by blocking the absorption of fat in the gastrointestinal tract, is an over-the-counter version of Xenical, a prescription diet medication available since 1999.

Wolfe requested that the FDA reject Orlistat as an over-the-counter drug because studies showed that Xenical caused precancerous lesions in rodents.


He noted that people taking the drug should expect to lose only about 6 pounds more than they would by dieting alone - and that its side effects include flatulence, greasy stools and occasional loss of bowel control.

"It's a very irresponsible idea, to approve this over the counter," Wolfe said.

Hinish sees another potential problem. By blocking the body's absorption of fat, the pill may also block absorption of fat-soluble nutrients such as vitamins A, D and E and omega-3 fatty acids that offer health benefits.

"Blocking fat absorption is an old philosophy of weight loss that doesn't hold true anymore," Hinish said.

But Glaxo officials argue that the medication has been on the market in prescription form since 1999 and was subjected to four years of human trials before it was approved. The firm plans to advise customers who take the pill to go on a diet, take supplementary vitamins and exercise regularly.

"The FDA has reviewed those concerns and they're completely invalid," said Malesia Dunn, a Glaxo spokeswoman.


The FDA also is reviewing a prescription diet drug with the generic name of rimonabant, marketed by Sanofi-Aventis, and approved for sale last year in Europe.

Marketed as Acomplia, the drug blocks receptors in the endogenous cannabinoid system, which regulates how we use and store food energy, so that it curbs our appetites, company officials say. Sanofi hopes to win FDA approval in late July.

Rimonabant has a high media profile because it's the first to block the cannabinoid receptor system.

In clinical trials, those who took rimonabant for a year, along with participating in a diet and exercise program, lost only 7.9 pounds more than those taking a placebo - and some patients reported depression and anxiety as side effects.

"It's a good drug, but it's not going to be a blockbuster," said GW's Frank.

Frank said he has not seen benefits from any of the dietary supplements that promote weight loss but don't have to undergo FDA reviews before they're sold.


"There's a whole bunch of stuff you can buy at a health food store. None of it works," he said. "If it really worked, they'd be lining up to buy it."

Still, Frank is optimistic about the prospects for future weight loss medications. Someday, he predicted, we will be able to regulate brain signaling with medication that controls our eating - the way we now can regulate our blood pressure and control cholesterol levels, he said.

"Everything we're doing now will be obsolete in 10 years," he said.

Until then, most people will still have to do it the same way as Ryan, who lost the equivalent of a full-sized adult.

For Ryan, a 63-year-old nurse practitioner who now weighs 150 pounds, it was a matter of diet and exercise.

"I just thought to myself, 'I don't want to be obese anymore,'" she said. "I'm waiting to see if the weight comes back."