BODY WATCH : Waist Away : A new generation of diet drugs is gaining favor among obesity experts. The long-term aids seem to be effective--and not addictive

No matter which diet Iris Golden tried, success was short-lived. Soon after shedding pounds, the 5-foot-2 owner of a Chicago executive search firm would return to her pre-diet weight of 250 pounds.

Michael Heald, 41, of West Hollywood, understands. At 30, his weight began to increase, topping out at 258 pounds and sticking like glue to his 5-foot-7 frame.

Today, Heald and Golden are both trimmer and, they say, happier. Golden, 57, is a Size 10 or 12 and no longer shops for pants with 44-inch waists. Heald, who works for a Los Angeles law firm, has dropped more than 50 pounds.

Both are disciples of an investigational new treatment approach that views obesity as a chronic medical problem, not a willpower deficit. Every day, Golden and Heald take medication to control their weight. They also eat a healthful low-fat diet and exercise moderately.

“It’s becoming apparent that obesity is a regulatory problem of body fat, just like hypertension is a regulatory problem of blood pressure or diabetes is a regulatory problem of sugar,” says Dr. Frank Greenway, a UCLA associate clinical professor of medicine and a leading national obesity researcher.

Like many hypertensives and diabetics, obese people need chronic medication, Greenway and others contend, not the traditional 12-week regimen of appetite suppressants usually prescribed.

Not everyone agrees with this new pill-a-day approach, but it is gaining favor, especially among obesity experts. At the 7th International Congress on Obesity last month in Toronto, many research papers focused on these so-called new generation diet drugs.

Among the medicines under study are a new combination of two old appetite suppressants, antidepressants and a drug that lets some fat from foods pass right through the body. Some drugs under study could be approved as obesity treatments in three years or less, researchers estimate.

Traditional diet drugs have a bad reputation, Greenway says, based on older generation medicines that could be addictive and cause people to get “jittery.” But the newer medications are not addictive, he says, and have been studied for longer terms.

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This interest in long-term diet medications is peaking at a time when obesity is rampant and failure is the norm in weight maintenance. About 30 million Americans are obese, defined roughly as being 20% or more above ideal weight. Obesity may increase risk for heart disease, diabetes, osteoarthritis and other ailments.

About 95% of those who enroll in organized weight loss programs regain the weight, according to the National Institutes of Health, most within one to three years.

The pill-a-day approach received a big boost two years ago when a University of Rochester study of appetite suppressants, published in Clinical Pharmacology and Therapeutics, was picked up by the press. In short order, 5,000 requests for more information flooded the university, recalls spokesman Robert Loeb.

In the study, a new combination of two old appetite suppressants, phentermine (Ionamin) and fenfluramine (Pondimin), helped some of the 121 subjects lose weight when they also followed a program of dieting, exercise and behavior modification, found Dr. Michael Weintraub, formerly at the University of Rochester and now director of the Food and Drug Administration’s Office of OTC Drug Evaluation.

During one 34-week phase, subjects assigned randomly to appetite suppressants lost 32 pounds on average while those assigned to placebo pills lost only 9 pounds. Then doses and regimens were varied. Taking suppressants intermittently didn’t work as well as taking them continuously. Some on the suppressants maintained the loss for as long as they remained on the regimen, which was up to 3 1/2 years.

Not all patients lost weight and there were some side effects--most common in the early months--such as dry mouth, nausea and diarrhea.

Fenfluramine affects a brain chemical called serotonin; phentermine affects chemicals called catecholamines. “They both cause people to eat less and to lose weight,” explains Dr. Richard Atkinson, professor of medicine and nutritional sciences at the University of Wisconsin, Madison.

During the last 20 weeks of the four-year study, when everyone discontinued the medication but kept dieting and exercising, “almost everyone regained all the weight,” Weintraub found.

For the past two years, Dr. Roy Blank, an internist in Charlotte, N.C., has supervised more than 1,200 people on the same regimen used by Weintraub, getting government approval to do so. (In many states, use of these drugs for more than 12 weeks is illegal.) At the one-year mark, his subjects--the vast majority women--have lost on average about 15% to 20% of their beginning body weight. Besides taking the daily medication, his subjects follow a 1,200 to 1,500 calorie diet and exercise moderately for about two hours a week.

“The key point is, these medicines are a supplement to what else we are doing,” Blank says. The drugs cost his patients about $50 a month. (Other researchers can’t say for sure what their regimens will cost once approved.)

Blank warns potential subjects about the possibility of gallbladder problems, associated not with the medicines per se but with the weight loss. “In the last two years, 22 people have had to have their gallbladders removed,” he says. In addition, depression became so severe in about 30 patients, he says, that they were taken off the diet drugs and placed on antidepressants.

Blank is collaborating on the analysis of his data with Atkinson, of the University of Wisconsin and a well-known obesity researcher.

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Meanwhile, others are studying sibutramine, originally developed as an antidepressant. A two-year study, involving 1,050 patients, is now entering the second year at seven sites, says Greenway, one of the investigators. The highest sibutramine dose given--30 milligrams a day--has resulted in a 20-pound weight loss at the six-month mark, says Greenway, with weight loss continuing after that time. The sibutramine, he adds, “might work like a combination of fenfluramine and phentermine.” Insomnia is often reported as a side effect.

Another antidepressant, Prozac (fluoxetine), might also suppress appetite. After studies suggesting its value as a weight control aid, Prozac’s manufacturer, Eli Lilly and Co., sought Food and Drug Administration approval in 1988 to market it under the brand name Lovan as an obesity treatment, a representative says. But the request has not yet been approved, says FDA spokeswoman Susan Cruzan.

The Lilly request is controversial because some who took the drug for depression have sued, claiming it can lead to violent behavior and even suicide attempts. But physicians who prescribe it regularly claim that those reactions are in the minority. Lilly contends that violent behavior does not increase with the drug’s use.

Another drug, orlistat, works by minimizing the amount of fat absorbed from food, says a representative for Hoffmann-La Roche, the developer. Orlistat binds to pancreatic lipase, an enzyme secreted by the pancreas to help break down fat. As a result, about a third of a dieter’s fat intake passes undigested through the body. Studies are continuing.

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Not everyone believes long-term medication is the answer. Treating obesity can do more harm than good, psychologist Janet Polivy of the University of Toronto told participants at the Congress on Obesity.

“Because we do not know how to define which sorts of obesity are medically dangerous, decisions to treat are based more on weight than on actual risk,” she says. The obese should obtain a physical exam to rule out other causes of excess weight, Polivy says, and then should “evaluate their eating and their exercise and find a weight appropriate for them.”

Even advocates of the approach urge caution.

The regimens are all considered investigational, Greenway points out. “If you want in on this,” he suggests, “get involved in a trial”--in which patients are closely monitored for progress or side effects.

Agrees Atkinson: “These drugs should be used as part of a research project. This does not mean private practice doctors can’t prescribe (them).” Rather, Atkinson urges obese patients to find doctors well-acquainted with the new approach and who work with researchers to document findings and patient progress.

* For a five-page summary and update of the original 68-page University of Rochester Diet Study, send a self-addressed, stamped, business-size envelope and $2 cash or check to Diet Study, University of Rochester Medical Center, P.O. Box 633, Rochester, N.Y. 14642.