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Weight Loss: The Spirit Is Willing -- But Pills Work


For more than a decade, magazines, books, and innumerable diet gurus have nagged us to exercise more and eat less, to no avail. A third of U.S. adults are now obese, compared with 23% in 1994. Americans may set great store by a can-do spirit, but in this critical area, we can't. "Overweight or obesity seems almost inevitable in adulthood," laments an editorial in the Feb. 15 issue of the Journal of the American Medical Assn. (JAMA). We live in a society that does everything it can to encourage a ceaseless march toward the far side of the scale. As a result, a consensus is forming in the medical community: Putting pressure on obese patients to exercise and diet is all well and good, but pills are more likely to take off the pounds.

One pill in particular is on the cusp of winning marketing approval, and it is already galvanizing the weight-loss community. Acomplia, from Sanofi-Aventis (SNY), blocks brain signals that stimulate food cravings, with minimal side effects. A study in the Feb. 15 JAMA found that 46% of obese patients who took Acomplia for two years were able to lose 5% to 10% of their body weight and keep it off. Granted, the dropout rate was high (51% of patients quit the trial before a year was out) and the weight loss doesn't sound like much if your starting point is 300 pounds. But health experts say that even morbidly obese people can greatly lower their risk of diabetes and cardiovascular disease with a 5%-10% weight reduction.

Doctors who treat the weight-challenged will be prescribing the drug with some regret. "I would love to see people turn this around with a change of behavior," says Roger D. Cone, director of the Center for the Study of Weight Regulation & Associated Disorders at Oregon Health & Science University. Our bodies hate behavioral changes, however, and can overcome the best of intentions by fighting hard to keep fat stores constant. Studies have found that 95% of people who lose weight put it back on within three years. "The need for better solutions is huge, and medication will play a role," Cone acknowledges.

BLOCKBUSTER POTENTIAL

Even patients who lost weight with Acomplia weren't home free. Those who went off the drug regained it all. The pill would therefore have to be taken for years to be effective. That's a recipe for a blockbuster. Some investment analysts estimate that Acomplia sales could total $4 billion within two years.

The drug has only two rivals on the market now: Abbott Laboratories' (ABT) Meridia, an appetite suppressant, and Roche Holding Ltd.'s Xenical, which prevents fat absorption. But Meridia can increase blood pressure, and Xenical causes diarrhea -- side effects that limit the products' usefulness. Doctors are calling for better medications, and the industry is listening: At least 60 weight-loss medications are currently in development.

Their time has come. An estimated 65% of U.S. adults are overweight or obese, and almost 20% of children. "We live in an 'obesity-genic' environment," says Dr. George L. Blackburn, associate director of the Nutrition Div. at Harvard Medical School. "[It's] driving us to the inevitable, the entire population becoming overweight."

This environment is constructed out of extremely cheap calories. Waistlines in the U.S. started expanding dramatically only 25 years ago; in 1980, just 46% of adults were overweight. A 2003 study by three Harvard University economists, David M. Cutler, Edward L. Glaeser, and Jesse M. Shapiro, found that Americans are as active these days as they were in 1970, so sedentary lifestyles alone aren't to blame. Rather, we are eating 200 calories more a day than we did 10 years ago, which can add 20 extra pounds a year.

TERRIBLE TEMPTATION

The Harvard study concluded that improvements in processing, the rise of fast-food restaurants, and the huge variety of convenience dishes have made calories inexpensive, plentiful, and deadly. One bad player is high-fructose corn syrup, a cheap and easy-to-use alternative to granular sugar that is also metabolized differently. Corn syrup gained popularity in the 1980s and now accounts for more than 55% of the sweetener market. Studies have correlated its use with skyrocketing rates of Type 2 diabetes. Cheap, tasty food "has put us in hedonic overdrive," says Dr. George Bray, an obesity specialist at Pennington Biomedical Research Center at Louisiana State University. "I conclude that this trend is unstoppable."

Doctors do harbor plenty of concerns about handing out weight-loss pills, especially to people who are only slightly chubby. They remember fen-phen, a diet pill combination whose use exploded in the mid-1990s. Some 14 million prescriptions were written in 1995-97, before fen-phen was discovered to cause fatal heart problems and was pulled from the market.

Acomplia seems well-tolerated so far. But what if the drug were taken for years? "We have no idea what the side effects would be," warns Dr. Denise G. Simons-Morton, an obesity specialist at the National Institutes of Health. She would prefer to see society change in ways that would emphasize an active lifestyle, smaller portions, and other forms of prevention, but "I don't see much going on" in that direction. Until there is, for most of us the choice may lie between a pill and a plus size.

By Catherine Arnst


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