There's no pill for svelte. Despite abundant advertising hype, no drug (and no "natural" herb or mineral) offers a magic bullet against obesity. Still, some relatively new drugs may provide useful support in a balanced weight-loss program.

This may not sound exciting, but it's the brightest prospect for weight-loss drugs in decades--except for a brief period in the 1990s. Then, a combination of drugs known as "fen-phen" seemed to offer astonishing promise but turned out to be more bullet than magic when some patients developed heart-valve disorders.

Now, three different prescription drugs have proved themselves as useful weight-loss aids, at least for some patients. But they're not panaceas. The drugs will only work as part of, not instead of, a lifestyle-change program that emphasizes diet and exercise.

"Although Americans would like to have a pill to cure obesity, the best that will ever be available is something that will contribute to a lifestyle effort and make it less of a struggle," says Madelyn Fernstrom, PhD, director of the Weight Management Center of the University of Pittsburgh in Pennsylvania.

By Prescription Only

The three most-prescribed prescription drugs are:

* Xenical (orlistat), approved by the Food and Drug Administration (FDA) in 1999. It interferes with the digestion of fats and prevents about 30 percent of the fat that you eat from being absorbed by your body.

* Meridia (sibutramine), approved in 1997. It boosts the levels of two neurotransmitters--norepinephrine and serotonin--in your brain to moderate hunger pangs and give you a feeling of fullness.

* Phentermine (available under several brand names including Ionamin and Adipex-P), approved in 1957. Phentermine suppresses appetite by boosting norepinephrine levels. It is approved only for short-term use. However, many physicians prescribe it for intermittent use over longer periods.

Phentermine was the "phen" in fen-phen, but it was not implicated in the heart-valve disease that a small but significant proportion of fen-phen users developed. Nor was the fen-phen combination ever formally approved by the FDA or packaged as a single product.

Instead, favorable clinical-trial results in the early 1990s led many physicians to combine prescriptions for phentermine with either the appetite-suppressant fenfluramine or its close cousin dexfenfluramine--the "fens." By 1997, about six million patients had used the combination.

That year, physicians began to report clusters of valvular heart disease among fen-phen users. The FDA urged patients to stop taking the fenfluramines, and the manufacturer, American Home Products, pulled them from the market.

Since then, American Home Products has been besieged by lawsuits running into the billions of dollars.

Whether the fen-phen fallout has soured physicians on other weight-loss drugs is uncertain. "The litigious nature of our society has scared off many good-hearted primary care doctors," Fernstrom says. Even so, more than 2 million patients have been treated with Meridia, and more than 2.3 million have tried Xenical, according to the drugs' manufacturers, Abbott Laboratories and Roche Pharmaceuticals.

Other prescription drugs aimed at suppressing appetite are mostly amphetamines or amphetamine-related compounds. They are subject to abuse, can cause drug dependence, and are approved only for short-term use. Hence, they are prescribed much less frequently.

Over-The-Counter Options

Over-the-counter weight-loss drugs, those that consumers can simply pick up as they breeze through pharmacy diet sections, are no longer available. The FDA warned in November 2000 that the main ingredient of such drugs, phenylpropanolamine (PPA), could cause strokes, and the major manufacturers quickly recalled them.

A few PPA-containing preparations may be left on drugstore shelves, but for the most part, the only diet medications now available without a prescription are herbal and other "natural" preparations. Under federal law, these can be marketed without the proofs of safety and effectiveness required for FDA approval. Conventional physicians and researchers consider most of them useless and some of them dangerous. (See box on page 52.)

Herbal remedies are "not well supported at all" by clinical-trial data, says Belinda O'Connell, MS, RD, LD, a clinical dietitian at the International Diabetes Center in Minneapolis, Minn.

Supporting Studies

Xenical, Meridia, and phentermine, by contrast, have abundant clinical-trial support. Patients in a recent trial that combined Meridia with a highly restricted diet lost an average of 9.8 percent of their starting body weight--21.5 pounds--in the first three months (although nearly half of those who started the trial dropped out). Patients in five Xenical trials lost an average of 12.4 pounds after six months and 13.4 pounds after a year--better than twice the weight loss of patients who were given placebos (dummy pills).

In a recent, year-long trial involving people with type 2 diabetes, those taking Xenical not only lost more weight than patients taking dummy pills but also reduced their need for insulin.

The toughest part of losing weight, however, is holding on to your lower weight after the first six months or so. "The vast majority of people trying to lose weight on their own fail not to take it off, but to keep it off," Fernstrom says.

Xenical and Meridia recently proved effective in helping at least some patients keep weight off.

In two long-term clinical trials in Europe, 177 patients who had lost at least 5 percent of their body weight taking Xenical for 12 weeks were continued on the drug (and on a reduced-calorie diet) for an additional 92 weeks. At the end of the two years, more than half of the Xenical patients maintained 80 percent of the weight loss they had achieved in the first six months. On average, these patients lost 10.6 percent of their body weight during the two years. Patients taking placebo slimmed down by only 2.4 percent.

A two-year European trial of Meridia produced similar results. In that trial, 467 patients lost more than 5 percent of their body weight in the first six months. They were then divided into treatment and placebo groups, and the trial went on for another 18 months. At the trial's end, 204 Meridia-treated people had stayed with it. Eighty-nine of those (43 percent) maintained 80 percent or more of their original weight loss. Only nine of the 57 people in the placebo group (16 percent) held onto their original weight loss that well.

Limitations And Risks

Unfortunately, the drags don't always work. If patients don't lose weight in the first few months, experts caution, the drags won't do any good and should be stopped.

Some people shouldn't take them at all. The drags aren't designed for cosmetic dieting. They should be used only by the obese or near-obese--people with a body mass index (BMI) of at least 30, or of 27 if they have other risk factors such as diabetes or high blood pressure.

Furthermore, these are powerful drugs, with significant potential side effects, and they should not be taken without a doctor's supervision.

Meridia and phentermine, which act on brain chemistry, may increase blood pressure, can interact badly with some antidepressants, and may cause an array of discomforts including dry mouth, headache, and constipation. They also may affect cognitive and motor skills. In other words, be careful about driving when taking them. Phentermine, an amphetamine-derivative, can cause drug dependence.

Meridia's and phentermine's FDA-approved labels also warn that physicians should watch their patients who use these drags for signs of primary pulmonary hypertension--abnormally high blood pressure in the arteries of the lung that eventually can weaken the heart and lead to heart failure--even though the disorder has not been directly linked with either drug.

Xenical's side effects are quite different because it operates in a unique way. The drug partially blocks the action of digestive enzymes known as lipases that help your body break down fat. As a result, your body absorbs only about 70 percent of the high-calorie fat that you eat; the rest passes through your intestinal tract undigested.

But Xenical also can block the absorption of some vitamins, such as vitamin E, and may affect others. So if you use Xenical, you should also take a multivitamin. The drug also interferes with the immunity-suppressing drug Neoral (cyclosporine), which is frequently given to organ-transplant patients. It can cause some urinary problems.