Lemons for Weight Loss

Right after residency, I took a summer job in a family practice in a beach town on Long Island, covering Fridays and weekends for the regular doctors. The setting was quite different from my training in an urban hospital. It was a bit of a culture shock to go from a world of critically ill hospitalized patients to an outpatient suburban setting where most weekend appointments were for sore throats, rashes and sprained ankles. But I quickly became a pro at Lyme disease identification.

One day, a woman in her early 40s came for an appointment. She asked me to prescribe fen-phen, a weight-loss pill that combined the drugs fenfluramine and phentermine and was being heavily marketed at the time.

I remember gazing at her from across the desk, thinking that she certainly didn’t look overweight, and asked her why she wanted weight-loss pills.

She grasped the skin around her stomach and said ruefully, “I’ve been trying to get rid of these extra pounds after having kids.”

I leaned over to see what she was holding in her grip. It looked like a normal amount of stomach to me.

Having just spent the past three years taking care of critically ill hospital patients who were dealing with heart attacks, septic shock, pneumonia and bleeding ulcers, I had a hard time seeing a few extra pounds as a medical issue. I was also a little leery of the whole idea of weight-loss pills, which seemed like a Band-Aid approach to what was usually a lifetime pattern of poor eating habits and inactivity.

I started to explain my concerns, noting that every medication has side effects. But before I could even get to any discussion about diet and exercise, she cut me off.

“I’ve taken fen-phen before,” she said, her voice more harsh now. “I just need a prescription from you, not a lecture.”

I was taken aback by the vociferousness of her response. I scanned her chart to see if she’d been heavier in the past. She hadn’t. In fact, she was quite healthy, with no major medical problems. I wondered if she might have an eating disorder that might alter her perception of her weight.

But we never got that far. When I reiterated my hesitations about prescribing pills for weight loss, she grew angry and stormed out in a huff.

A month later, The New England Journal of Medicine published an article linking fen-phen to heart valve abnormalities. Shortly after, the medication was pulled from the market. I wanted to feel vindicated, but I knew that during my tense exchange with my patient I hadn’t had any clinical premonitions about the drugs’ dangers, just a sense that she didn’t really need weight-loss pills.

This encounter came to mind recently when I read an essay called “Lemons for Obesity” in Annals of Internal Medicine. The author, Dr. Michael S. Lauer, was one of only two members of a 22-member Food and Drug Administration panel who earlier this year voted against approval of the new weight-loss drug Qnexa, a combination of phentermine and topiramate, an epilepsy drug with an unexpectedly salubrious side effect of weight loss.

Final approval of the drug has been delayed, but in the essay, Dr. Lauer gives a brief history of Qnexa’s approval process, including concerns of cardiovascular side effects and possible risks of cleft lip and cleft palate in babies born to mothers taking the drug. Then he makes an interesting analogy to the used-car market, citing the 1970 paper “The Market for Lemons” that eventually won a Nobel in economic science for its author, George Akerlof.

Lemons are harder to sell than quality products, so sellers do more promotion and offer steeper discounts, Dr. Akerlof had argued. In addition, used-car buyers (like patients) know much less about the product than used-car sellers (and pharmaceutical companies). Lay people rarely have much success when looking under the hoods of either cars or medicines. This combination of “information asymmetry” and aggressive marketing can allow lemons to dominate the market.

Dr. Lauer lists the impressive number of lemons for treating obesity. Fen-phen, ephedra, sibutramine and phenylpropanolamine all had to be pulled from the market for safety concerns. A drug popular in Europe, rimonabant, was denied approval in the United States because of side effects. The lone prescription drug currently available in America for weight loss, orlistat, offers only minor weight loss with the trade-off of major stomach problems in the form of oily, greasy stools.

The weight-loss field is strewn with lemons, more so than other areas of medicine, Dr. Lauer argues. Because of the enormous potential market for these drugs — two-thirds of American adults are overweight or obese — pharmaceutical companies rush new drugs to market after conducting only small clinical trials. The F.D.A. and doctors are complicit in the process, Dr. Lauer says, leaving the population at large to act essentially as guinea pigs.

Dr. Lauer cites another intriguing paper from the 1970s, by Amos Tversky and Daniel Kahneman, that highlights our biases when interpreting data, especially from small studies. There is an “illusion of validity” for any random data point, a seductive sense that is colored by what we hope will be true. Mountains of pharmaceutical claims are often made from mere molehills of data.

In the decades since my encounter with the patient who demanded fen-phen, I’ve become a lot less smug about the problem of obesity. I appreciate that there are factors at play beyond diet and exercise, but the “lemon lesson” has stayed with me. It’s hard to know at the outset which new drugs are lemons and which will become game-changers. But any drug that arrives on the scene with heavy promotion and only modest benefits deserves the same circumspect attitude as that too-good-to-be-true used car. (from the New York Times)