Diet drugs work: Why don't doctors prescribe them?

The woman sat down on my examination table and pointed to her tight paper robe.

"Doctor," she said, "I need your help to lose weight."

I spent the next few minutes talking to her about diet and exercise, the health risks associated with obesity, and the benefits of losing weight, a conversation I have had with my patients for over twenty years. But like most Americans, most of my patients are overweight.

After that, I realized that my patient wanted a pill that would make her lose weight. I could prescribe her one of four drugs currently approved by the F.D.A.: two, phentermine and orlistat, which have been around for more than a decade, and two others, Belviq (lorcaserin) and Qsymia (a combination of phentermine and topiramate), which have recently come on the market and are the first drugs approved for long-term use. (Ian Parker wrote about the Federal Food Administration's approval process for new drugs in this week's issue.) These drugs work by suppressing appetite, boosting metabolism and other mechanisms not yet fully understood. These new drugs, as well as beloranib, which provides greater weight loss than all currently available but is still in clinical trials, were discussed with great enthusiasm last month by experts and researchers at the international Obesity Week conference in Atlanta.

But I've never prescribed diet drugs, and few physicians in my primary care practice have either." Donna Ryan, an obesity specialist at the Pennington Center for Biomedical Research at Louisiana State University, found that only a small percentage of the physicians she surveyed regularly prescribed any of the drugs currently approved by the federal Food Administration. Sales data show that physicians also have not taken the new drugs, Qsymia and Belviq.

The unfavorable history of diet drugs undoubtedly contributes to the reluctance of doctors to prescribe them. In the nineteen-forties, when doctors began prescribing amphetamines for weight loss, there was a dramatic increase in addiction. Then, in the nineties, fen-phen, a popular combination of fenfluramine and phentermine, was taken off the market when patients developed serious heart defects. Modern drugs are much safer, but they produce only a modest five to ten percent weight loss, and they have side effects.

Nevertheless, as Ryan pointed out, doctors don't always shy away from prescribing drugs that cause side effects and don't produce dramatic results. Losing five to 10 percent weight may not get patients excited or even out of overweight or obesity, but it can improve control of diabetes, blood pressure, cholesterol levels, sleep apnea and other complications of obesity. And while these drugs are not covered by Medicare or most states' Medicaid programs, private insurance coverage for weight loss drugs has improved and is likely to expand even further under the Affordable Care Act, which requires insurers to pay for obesity treatment. So what's stopping doctors from prescribing these drugs?

Several of the leading experts and researchers who participated in Obesity Week told me that the problem is that while obesity experts view it as a chronic but treatable disease, primary care physicians are not completely convinced that they should treat obesity at all. Although doctors have known since the time of Hippocrates that excess body fat can cause disease, the American Medical Association announced only a few months ago that obesity was recognized as a disease. These divergent views on obesity represent one of the widest gaps in understanding between generalists and specialists in all of medicine.

Lee M. Kaplan, co-director of the Massachusetts General Hospital Weight Center, believes that some of the bias stems from the fact that the average physician does not understand the complex physiology of weight homeostasis. Humans have evolved to avoid starvation, not obesity, and we protect our body weight through a complex system involving the brain, gut, fat cells and a network of hormones and neurotransmitters, only some of which have been identified. According to Kaplan, obesity, which is a dysfunction of this system, is probably not one disease but dozens.

The fact that one person's obesity is not like another's may explain why some people lose a lot of weight with surgery, a certain diet or medication, and some do not. Kaplan believes that if more doctors understood this, they would be more receptive and realistic about treating obesity. He said: "If I told you, 'I have a drug that treats cancer,' and you asked me, 'What kind of cancer?' and I said, 'All kinds of cancer,' you would laugh, because you intuitively understand that cancer is a heterogeneous group of diseases. Someday we'll look back on obesity and say the same thing."

Obesity is potentially, in part, a neurological disease. Jeffrey Fleier, an endocrinologist and dean of Harvard Medical School, has shown, as have others, that constantly eating more calories than you burn can damage the hypothalamus, an area of the brain involved in the process of eating and satiety. In other words, Big Gulps, Cinnabons and Whoppers have altered our brains so that many people, especially those with a genetic predisposition to obesity, find it almost impossible to give up fatty foods if they have eaten enough of them. Louis J. Aronn, director of the Comprehensive Weight Control Program at New York-Presbyterian/Will Cornell Medical Center, explained it to me,

"With so much available caloric food, hypothalamic neurons become overloaded, and the brain cannot determine how much fat is already stored in the body. In response, it tries to store more fat. So there is very strong scientific evidence that obesity is not due to lack of willpower."

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