In the mid 1990s I attended a conference on medical treatment of obesity where many of the participants were nearly giddy with excitement. The FDA had just approved Redux (fenfluramine), an appetite suppressant which, combined with an older drug, phentermine, became the wildly popular "Fen-Phen." Doctors listened eagerly to lectures about this drug, which might help patients lose weight as no mere diet or exercise program ever had. Some physicians spoke of abandoning their practices to open weight loss clinics in which Fen-Phen, and eventually even more effective drugs, would become the centerpieces of state of the art obesity treatment.
A few months later, Redux was pulled from the market after fenfluramine use was associated with potentially lethal heart and lung damage. A decade later, the newer drugs simply haven't arrived, or they've arrived and produced only modest weight loss at the cost of frequent side effects. Why? Given that more than half of all Americans are overweight and that Americans take prescription drugs so commonly (three quarters of people over fifty do so, according to one study) it is surprising that there is so little news about prescription drugs for weight loss.
One reason may be that the causes of obesity are too numerous and too varied for any one drug to address. Genetic, neurochemical, psychological, social, environmental, hormonal, and other factors all contribute to extra weight. A drug which suppresses appetite might have limited effect if you routinely overeat when you aren't hungry (as many people do). A drug that blocks fat absorption may not help much if you are inundated with sugary, but low-fat, carbohydrates.
Diet drugs have gotten a lot of press recently because of the approval, in June of 2007, of Alli, an over-the-counter version of the fat-blocking drug orlistat (Xenical). Alli, discussed here in a previous blog, works by blocking fat absorption in the intestines and must be taken before every fat-containing meal.
Many physicians and patients were also enthusiastic about rimonabant (Acomplia), a drug that works by blocking the same receptors in the brain that cause the "munchies" in marijuana users. Rimonabant is currently available in many European countries. But in 2007, a federal advisory committee recommended against the drug's approval in the U.S., citing concerns that rimonabant may leave people vulnerable to neurological and psychiatric problems?including a higher risk of suicide. Other prescription weight-loss drugs include those that suppress or regulate appetite by altering levels of brain chemicals ? namely, sibutramine (Meridia) and phentermine (Adipex, Ionamin, others).
The currently available drugs all produce modest weight loss (less than 10% of total body weight) and none are approved for long term use. Moreover, Meridia can cause hypertension, Xenical (and Alli) can interfere with the absorption of Vitamins A, D, E, and K, and phentermine can cause palpitations.
One way to minimize the risks of these drugs is to prescribe them only for people who need them for health reasons: those who have obesity-related conditions such as type 2 diabetes or hypertension, or those at high risk for developing such disorders. Even the small amount of weight loss produced by medications may be helpful to such people. One study of women with obesity demonstrated that those who intentionally lost any amount of weight experienced a 40%?50% decrease in death from obesity-related cancers and a 30%?40% decline in death from type 2 diabetes.
Guidelines issued by the National Institutes of Health (NIH) advise that weight-loss drugs be given only to people with a BMI of 30 or more, or ? in the case of those with weight-related health problems ? a BMI of 27 or more. The use of diet drugs by people with lower BMIs is likely to pose more risks than benefits.
Drug therapy works better when it's paired with an overall program of lifestyle change. A study published in 2005 in the New England Journal of Medicine showed that after one year, Meridia users who participated in a comprehensive counseling program that promoted a low-calorie diet and 30-minute daily walks lost twice as much weight as subjects who received counseling alone or Meridia alone
You can bet that with one third of Americans now obese (and at least 4 million over 400 weight, by recent estimates) researchers are working furiously to develop effective drugs to treat obesity - whether for the public health benefits or the enormous profits to be made with such drugs. But it seems to me that elusiveness of a pill to "cure" obesity begs a question: Is obesity really a disease? And, if it is, would our efforts in combating it be better focused on making public transportation, recreation facilities, and unprocessed foods more available rather than developing more drugs? What do you think?
Dr. Suzanne Koven practices internal medicine with a special interest in weight issues at Massachusetts General Hospital in Boston, and teaches at Harvard Medical School.
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