Weighing In With a New Pill

Xenical, the new prescription fat-fighting pill due to arrive this week in pharmacies nationwide, is already getting mixed reviews. Many who are trying to lose a lot of weight are understandably eager to take the pill, approved by the Food and Drug Administration last month, because it blocks an enzyme in the gastrointestinal tract and decreases absorption of dietary fat by about 30%.

Obesity specialists, although generally predicting a brisk business for Xenical (orlistat), don't expect it to beat out other options to become the only, or even the leading, star in the war on obesity. The real hope for effective obesity treatment, experts say, lies not with Xenical or any other single drug but with the host of drugs yet to come that will ultimately make up the smorgasbord necessary to best treat a complicated disease.

The next new obesity drug is probably two years, perhaps four, from FDA scrutiny, observers say. Among the contenders are drugs that suppress appetite or rev up metabolism.

Most often mentioned as a fat-fighting advance is leptin, the so-called anti-obesity hormone. First discovered in mice, leptin is made in fat cells and then circulates in the body and is believed involved in food intake and body weight regulation. In lab studies, mice deficient in leptin became obese and then shed weight when given leptin.

Amgen Inc., in Thousand Oaks, conducted widely publicized human studies of leptin. But ultimately, very few humans were genetically deficient in leptin. So Amgen and other companies are changing research direction.

The problem, says Lou Tartaglia of Millennium Pharmaceuticals in Cambridge, Mass., may be one of leptin resistance in the body. Now, Millennium is working to develop leptin in pill form to activate the leptin receptor in a way that the leptin of some obese people can't, so appetite can be suppressed and metabolic rate boosted.

Late last month, Amgen announced it is abandoning its development of the first form of leptin it studied and moving on to second-generation molecules. Also under study is enterostatin, a substance produced in the pancreas that signals the brain that one is full and may curb an appetite for high-fat foods.

Researchers at Pennington Biomedical Research Center at Louisiana State University suspect that lean people secrete more enterostatin than do obese people and have recently begun human studies of the peptide, says Dr. George Bray, an obesity specialist there.