(FORTUNE Magazine) – Americans are so aware of their weight that even brownies on the grocery shelves cry "fat free" to catch the attention of the righteous, and closets across the land are stocked with jogging shoes. So the U.S. must be shedding ugly pounds by the millions, right? Unfortunately, no. The surprising and depressing reality is that the nation's collective girth has ballooned over the past decade and a half. When Americans stepped on the scale in 1980, a quarter were overweight. Now the rolls of the fat have swollen to one-third of the population.

But there's also some soothing news for the nation's bulging paunch. Many medical experts believe they have found a safe and effective weapon against obesity in a selection of drugs. One treatment has become so popular that physicians have quadrupled the number of prescriptions they write for it. In the next year or so, the Food and Drug Administration--so cautious that it hasn't approved a new diet drug in 23 years--may allow several new ones to go on the market. And just over the horizon, maybe, is an innovative generation of treatments based on accumulating knowledge about the genetic roots of obesity.

The potential for the pharmaceutical industry is enormous. Consider: About 58 million adults carry enough extra weight to put them at some health risk. Not all of them will want--or qualify for--drug treatment, but enough will so that Wall Street is smelling the bacon. When scientists working on a gene owned by Amgen announced in July a protein that made mice lose weight, the market capitalization of the dynamic biotech company jumped by over $900 million, to $11.2 billion.

What's driving this new enthusiasm for drugs is a growing conviction among many doctors that obesity is a disease. Backing them up is increasing evidence that genetic factors account for a sizable part of the national obesity crisis. Many people seem to be genetically misprogrammed for an era of abundance; they lack the internal signals by which body and mind tell each other that the danger of starvation is long past--so drop the forks.

Because obesity is an illness, these authorities maintain, it makes sense to treat the condition not solely with diet and exercise but in many cases with drugs as well. What they have in mind is not just a quick series of pills to trim some pounds off. They want to prescribe long-term, perhaps lifetime, drug therapies, just as they might for hypertension. Obesity's victims, these doctors hope, will not only be able to take pounds off but will also keep them off forever.

What does one have to weigh to qualify as obese? That's difficult to say. Doctors have no precise definition of obesity. But if you think the paunch you've acquired or the hips you've padded since college are harmless, pay attention. Many medical experts maintain that if you have swollen to 20% above your ideal weight, you are living in a dangerous zone. "If we could get the entire population within 20% of ideal weight, we'd probably have 80% fewer cases of diabetes, which is a leading cause of kidney failure and heart disease," says Dr. Louis Aronne, director of the weight-loss center at prestigious New York Hospital--Cornell Medical Center. As many as 300,000 early deaths might be prevented annually--far more than the number dying each year from AIDS, drug abuse, and other high-profile killers--and the nation's health bill might drop by $70 billion.

The overweight men and women flocking to places like Biochemical Medical Care certainly feel pill-assisted slimming is just what the doctor should have ordered years ago. Housed in a nondescript gray-brick building in Monsey, New York, a leafy hamlet 25 miles from New York City, Biochemical is one of a number of recently opened weight-loss clinics that specialize in treating obesity with "fen-phen," a combination of the drugs fenfluramine and phentermine. Fenfluramine boosts serotonin, the same brain chemical that Prozac enhances to elevate mood, while phentermine mimics other substances in the brain. Together the medicines suppress appetite and speed the burning of calories. Fen-phen has rapidly emerged over the past three years as the heavy artillery in the battle of the bulge. Since Biochemical opened in March, some 700 people have signed on to its program, says co-founder Dr. Ronald DiScenza. Most return every few weeks for examinations and additional supplies of the prescription drugs.

On a recent evening Howard Hutson, 39, briskly strode into the clinic 69 pounds lighter than on his first visit in July, and sat down to wait for an exam with a dozen other determined-looking patients. He's hoping to subtract another 150 pounds from the 381 still straining his 6-foot 3-inch frame--a reasonable goal, he believes, now that fen-phen has checked his food cravings. Says he: "My main problem was always snacking and watching TV. Now I've started to push food away before finishing it."

Not everyone in the medical community is applauding the new therapies. Conservatives are aghast, worried that the new drugs are, in fact, more snake oil from the shamans of lite. Their concerns are understandable. A few decades ago amphetamines--"uppers" or "speed" as they're known in street slang--were widely prescribed to control weight. Patients got prettier figures but paid for them with raw nerves, higher pulse rates, and sleepless nights, symptoms that may have offset the medical benefits of fewer pounds. Conservatives also point out that risky as amphetamines were, they were generally prescribed only for temporary use. Advocates of new drug treatments leave open the possibility that the medicines will be prescribed for a lifetime.

Many conservative doctors, moreover, remain reluctant to diagnose obesity as a disease. In a 1987 survey of 318 physicians, two-thirds said their obese patients lacked self-control, and 39% described them as "lazy." That kind of analysis leads to a bracing, spartan argument that has considerable appeal to the puritan in all of us: Obesity results from a lack of discipline and can be corrected with diet and exercise.

Trouble is, that regimen hasn't worked, not yet at least. As a nation, like T.S. Eliot's J. Alfred Prufrock, we have wept and fasted, wept and prayed--collectively shedding millions of pounds. Indeed, at any one time about a third of us are dieting. We spend about $33 billion a year on super-low-calorie drinks, exercycles, diet books, fitness clubs, and such, but to no avail. A pound lost is generally regained in five years.

The conservative case seems to be losing ground in the medical establishment, not just because it has failed in practice but because it is wobbling a bit in theory as well. Last year a research group at Rockefeller University discovered in experiments on mice what has come to be called the obesity, or ob, gene. That revelation led to the identification of a hormone, dubbed leptin, that signals the brain how much fat is stored in the body. When injected into the rodents, the hormone lessened appetite and increased the burning of calories. Studies on ob have greatly boosted the credibility of the decades-old idea that the body has a fat thermostat whose level is largely determined by genes--and have also accelerated the race to develop drugs based on such genetic malfunctions (see box, "What Turns Mice Into Blimps").

The ob discovery was followed by a landmark report this spring from the Institute of Medicine, part of the National Academy of Sciences. An institute panel declared obesity to be a chronic disease, noting among other things that genes may account for a third of the variation in weight across the population. The report made a strong case for stronger remedies to address America's epidemic of obesity, including drug therapy. In a section urging the FDA to lower hurdles for approval of new drugs, the panel wrote that the U.S. has lagged "far behind other countries in the approval and use of anti-obesity drugs."

For now, the only diet drug commonly prescribed in the U.S. is the fen-phen combination that Howard Hutson and his comrades are taking. Doctors once prescribed it mainly for brief use by the "morbidly" obese (those who have a disease associated with their weight problem) to help shed pounds when all else failed. But in 1992 a widely publicized study at the University of Rochester showed that patients who took the drugs during a diet and exercise program dropped an average of 21 extra pounds, compared with those on a placebo, and kept most of the weight off for over three years while continuing on fen-phen. Soon after, demand for the drugs took off like the calorie count on Thanksgiving.

Says New York's Dr. Aronne: "I remember thinking, 'Medication? Never!' But when you see some of these patients and the results with drugs, it shifts the paradigm." Aronne and his colleagues still recommend diet and exercise, but drugs have definitely become part of the model recovery program. Capitalizing on the shift in medical thinking, two hefty players in the slimming business--Physicians Weight Loss Centers and Nutri/System--recently began offering fen-phen as part of weight-loss programs at physician-staffed centers. Revenues at Nutri/System's first four NutriRx centers doubled in a little over a month after they introduced fen-phen in September. Last month the chain opened five more fen-phen centers. (Both companies are privately owned and don't disclose revenues or earnings. But Diet Business Bulletin, an industry newsletter, estimates that Nutri/System had revenues of perhaps as much as $250 million last year, and Physicians Weight Loss about one-tenth that.)

Prescriptions are being written so fast that doctors and pharmacies in some places have recently had trouble getting enough fenfluramine, which is sold under the name Pondimin by American Home Products' Wyeth-Ayerst Laboratories division. Prescriptions of fenfluramine in 1995 are expected to be four times what they were last year, according to IMS America, which tracks pharmaceutical sales.

The excitement about fen-phen--and the anticipation of even better drugs--is not hard to explain. To the obese, their condition is devastating. They live in a world in which even the shapely think of themselves as too fat. Diligent researchers in Chicago and Toronto reported a significant slimming trend after 1959 among Miss America contestants and Playboy centerfolds. So imagine the despair of those who are double the size of what federal health officials call perfection. In a 1991 report on formerly obese people who had lost at least 100 pounds each, some 90% said they would rather be blind or have a leg amputated than gain back their excess pounds.

Deborah Bell, 48, of Gahanna, Ohio, considers fen-phen a miracle drug. For years she fought the good fight against fat--and lost. Anything but lazy, she would diet with steely resolve and shed 20 pounds, then gain back 30, lose 30 and gain 40, her self-esteem and willpower wilting as her weight inexorably rose to 220 pounds. "I was always the fat girl who tried to dress nice," she says. But by her mid-40s, the normally upbeat surgical nurse despaired. "As hard as you try, you find yourself standing in the kitchen eating."

This year Bell dropped 80 pounds and is holding steady at 140. Now she has to curb her gregarious streak: "When I was heavy, I could semiflirt with the men I worked with, and I was safe. Now I have to watch out." The credit for this wonderful problem, she says, goes mostly to fen-phen, which she's taken daily since February. Bell is participating in a five-year study at a Columbus weight-loss clinic on the use of the drugs to help prevent weight rebound after dieting. For her, taking fen-phen feels "like someone lifts this food demon out of your body. I got so excited at first when my food urges were controlled that I didn't eat enough and got scolded by my dietitian for skipping lunch."

For a couple of reasons, however, fen-phen is not the ideal and ultimate diet drug combination. First, there is some debate over safety. Most fen-phen researchers say the drugs pose minor health risks compared with amphetamines. For most patients the short-term side effects are offsetting--phentermine heightens alertness while persuading the body to burn more calories, and fenfluramine, thought to cut cravings for starches and sweets, can induce drowsiness. But some users experience a racing heartbeat and, although rarely, high blood pressure.

Some states ban fen-phen outright, and others limit the length of time a patient can take it. Says James R. Winn, executive vice president of the Federation of State Medical Boards: "The long-term use of diet drugs is extremely controversial. There's a strong likelihood weight clinics will abuse these drugs." And even though its effects are milder than those of amphetamines, the feeling of higher energy that fen-phen stirs can be habit-forming. Also, some patients who quit these drugs abruptly lapse into depression. Warns William Schmidt, an official of Ohio's medical board: "I have to tell you flat out that phentermine is abused. We've had a doctor lose his license because he became addicted to phentermine, and others have been disciplined for overprescribing it." Used alone, phen has enough kick to appeal to recreational drug users, who call it "bumblebee."

Some researchers assert that fenfluramine may damage nerve endings in the brain. There also are scattered reports of short-term memory loss among patients taking the drugs. A spokeswoman for Wyeth-Ayerst counters that fenfluramine has been used by 50 million people worldwide for a period of 30 years, yet no pattern suggestive of nerve damage has appeared. Fen-phen received some helpful support in September when an FDA advisory panel recommended that fenfluramine be dropped from the federal list of controlled substances.

Even so, fen-phen is not entirely effective. The Rochester study triggering the fen-phen stampede showed that over several years, subjects taking the drugs tended to regain some of the weight they had lost--albeit at a slower rate than those who didn't take them. Some people get no benefit from them. Says Judith Stern, a nutrition professor at the University of California at Davis: "We're at the same point with obesity drugs that we were with hypertension drugs in 1958, which weren't nearly as good as the ones on the market today."

The pace of progress may pick up soon. The FDA is considering an application by American Home Products to market the diet drug dexfenfluramine, which works on the brain in much the same way as fenfluramine but apparently more effectively and with fewer side effects. As with fen-phen, some researchers worry about animal studies that show heavy doses can cause nerve damage, a concern that in September erupted into a fiery argument before an FDA advisory panel. But dex has been used in Europe and elsewhere for ten years by about ten million people who have suffered no obvious harm. So there's a reasonable chance the FDA will allow it to go on the market in the U.S. next year. Approval would likely give a big boost to Interneuron Pharmaceuticals, the small Lexington, Massachusetts, biotech company that has developed the drug and licensed it to AHP. Interneuron, seven years old and publicly traded, had revenues of a mere $606,000 last year.

People who regard obesity as a disease can't wait to get their hands on these new--but still unapproved--drugs. In fact, some of them aren't waiting. When Eileen Marshall, a self-employed health care consultant in New York City, returned from a vacation in France this summer, she carried a year's supply of dex purchased at a Paris pharmacy. After her weight rose above 270 pounds, Marshall, 50, seemed a perfect candidate for fen-phen, because she lost pounds on diets but never kept them off, putting her on a collision course with the diabetes that runs in her family. But for her, fenfluramine caused intolerable diarrhea. After trimming 35 pounds on a weight-loss program last year, she decided to try dex.

Says Marshall, a composed, articulate woman who works from a home office on Manhattan's East Side: "If the FDA hasn't approved this drug when I run out of it, I'll have to go back to France and get some more. This is the first time I've been able to keep weight off without going crazy. I don't understand the thinking that it's okay to treat the effects of obesity with drugs but not the obesity itself." Finally, it seems, the medical community is catching up with her reasoning.