What if weight loss were as simple as popping a pill that limits your body's ability to absorb fat from food? By marketing such a drug over the counter, the pharmaceutical company GlaxoSmithKline is wagering that it can snag a chunk of the $41 billion Americans spend on weight-loss strategies each year. And after a thumbs-up from a Food and Drug Administration advisory panel in January, the agency granted conditional approval of the drug in early April 2006.

But ah, yes, there's a catch. The prescription version of the fat-blocking drug, orlistat (Xenical), hasn't lived up to its promise. "In clinical practice, we've found that compliance with orlistat is very poor because of its marginal benefit and tremendous side effects," said Zhaoping Li, M.D., Ph.D., of the clinical nutrition division at the UCLA Medical Center, one of the centers involved in the original trials of orlistat.

At half the prescription strength, the proposed over-the-counter version is likely to be even less effective while continuing to cause the negative effects of the eat-and-excrete approach to weight loss.

According to our analysis, total prescriptions for orlistat dropped by 65 percent between 2001 and 2005. In his comments to the advisory panel, Sidney Wolfe, M.D., director of the health research group of Public Citizen, a nonprofit consumer advocacy group, called the over-the-counter version of orlistat (to be named Alli) "a desperate attempt to revive a barely effective drug with an over-the-counter switch." There is too much short-term risk and no long-term benefit, so Public Citizen does not support the switch of orlistat to over-the-counter status, Wolfe said in a telephone interview.

Data presented to the FDA suggest that Alli works best in those who are very overweight and that results are modest. In clinical trials, severely overweight subjects taking the nonprescription dose for six months lost about 5 pounds more than those taking a placebo (the higher-dose group lost a bit more). In a separate four-month trial, moderately overweight people lost about 2½ pounds more than the control group. But any benefit is likely to be short-lived. Alli will be marketed for short-term (six months or less) use only. Follow-up suggests that people start to regain weight once they stop taking it.


embarrassing side effects

Although orlistat is generally considered safe, it's notorious for what one advisory panel member euphemistically termed "the underwear problem." Unabsorbed fat can cause intestinal side effects such as fatty stools, oily spotting, flatulence with discharge, an urgent need to defecate, and frequent bowel movements.

The drug can also impede the absorption of fat-soluble vitamins. Users are supposed to take a multivitamin at least two hours before or after taking the drug, but in actual-use studies, only about half managed to do so. Orlistat should not be used by those taking the blood thinner warfarin (Coumadin). People on diabetes medications should use it only under a doctor's supervision.

Once the maker of Alli meets the undisclosed conditions set out by the FDA, final approval is likely later this year. A six-month supply will cost about $300 to $650 and will be accompanied by material advocating a standard low-fat, reduced-calorie diet and exercise.

Alli may have won the advisory panel's support largely because it's the only game in town. "Obesity is such a huge public health problem," said panel member Neal Benowitz, of the division of clinical pharmacology at the University of California in San Francisco. "I'd rather have something out there with some evidence of safety and efficacy as an alternative to all those aggressively promoted dietary supplements that are not tested."

CR's take: Follow the diet advice, but skip the pills and save the money.