July 27, 1999 by Jim Dryden
Researchers today understand more about the problem of obesity than at any other time in history, but the number of obese Americans continues to increase. Although the search for effective treatments has intensified, only a small number of obese people lose their excess weight and keep it off.
Once thought of as little more than "letting yourself go," obesity now is treated as an illness that has genetic, behavioral, environmental and medical components. Researchers continue to learn about the balance between caloric intake and energy expenditure, but they admit that many aspects of obesity are poorly understood and that therapies often are unsuccessful in the long term.
Changes in lifestyle are the cornerstone of obesity therapy. Eating less and increasing physical activity usually help obese patients lose weight, and losing as little as 5 percent to 10 percent of total body weight can improve a patient's medical outlook by lowering cholesterol and blood pressure and by ameliorating diabetes and other conditions exacerbated by obesity.
Maintaining lifestyle changes and keeping weight off for life is a difficult proposition. But researchers at Washington University School of Medicine in St. Louis say drug therapy can help improve long-term results for properly selected patients. However, Samuel Klein, M.D., professor of medicine and director of the Center for Human Nutrition at Washington University's School of Medicine, argues in a June 1999 editorial in the American Journal of Clinical Nutrition that drug therapy may be most useful for maintaining rather than achieving weight loss.
Many patients think of medication as a first treatment. Most have tried all kinds of diets, and most have lost weight. But when the diet ends, the weight tends to come back. And unlike some patients with other chronic diseases, those with obesity are very aware of their problem. "If you have hypertension, no one may know it except you and your physician," Klein says. "If you have obesity, everybody knows it, so there is additional social pressure to lose weight. This pressure drives many patients to look to drugs as a possible quick fix."
The Food and Drug Administration has approved nine obesity drugs to date. Eight work by altering metabolism in the brain to suppress appetite and keep patients from feeling the need to eat. The ninth and newest, called Xenical (orlistat), prevents absorption of fat from the gastrointestinal tract. When compared with study patients who were given inactive placebos, about twice as many patients treated with Xenical had lost 10 percent or more of their body weight at the end of one year.
Klein says, however, that patients at Washington University's Weight Management Center are not considered for drug therapy until after they have participated in the program for at least six weeks. By that time, many already have lost significant amounts of weight. "Most patients would like a pill to make their disease go away, but no such pill exists for obesity, and our program steers patients to lifestyle changes instead," Klein says. "By the time our patients have been in our program for six weeks and are eligible for weight-loss drugs, many have made so much progress by changing their diet and increasing their physical activity that they no longer are interested in obesity drugs."
Maintaining lifestyle changes
But problems can develop when a program ends. Even in the most reputable programs, obese patients who lose 10 percent, 20 percent or even 30 percent of their body weight eventually are left without group meetings and other medical and psychological support services. Maintaining lifestyle changes gets more difficult then.
"During the first several months of the program, we provide behavior therapy, diet education and exercise training, and that is usually very effective in getting patients to lose weight. But maintaining the weight loss is much more difficult," Klein says. "Therefore, we consider drug therapy as a tool to help patients maintain their weight loss or to continue their weight loss if their body weight has stopped at an undesirable level."
But while Klein sees a role for obesity drugs, he says there is little research to show they will be effective over many years. Because most are relatively new, studies have looked at time periods of one to two years. "But obesity is a chronic condition that requires long-term therapy, and a trial that demonstrates efficacy for a year or two doesn't prove the drug will still be effective five, 10 or even 20 years later," he says.
Just as patients with hypertension, diabetes or other chronic illnesses can require therapy for a lifetime, Klein believes obese patients need to maintain their lifestyle changes forever and obesity drugs may help. But just as the first generation hypertension and diabetes drugs were not as effective as the medications developed later, Klein says future obesity drugs will be more effective. "The newer approaches will involve a better understanding of chemicals in our brain that regulate food intake as well as chemicals involved in burning up calories," he says.
In spite of the many molecular and behavioral contributors to obesity, a simple formula still applies, Klein stresses. To lose weight, people must burn more calories than they take in, a strategy that is made more difficult by sedentary jobs, elevators, cars and the easy availability of fast food. He says a person who sits at a computer all day, takes the elevator to the snack machine a few times each day and drives to the pizza place or hamburger joint for dinner and maybe a few beers is a good candidate for weight problems. Unless those behaviors change, he says, all the diet drugs in the world won't make that person thin.
Note: For more information, please refer to Klein S. "The War Against Obesity: Attacking a New Front," American Journal of Clinical Nutrition, 69(6), 1061-1063, June 1999.
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