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.
on 'Exercise' Pill
Many companies are hoping to develop a drug--in pill form--that would prevent neuropeptide Y, a powerful appetite stimulant in the brain, from sending its hunger signal, says Larry Brenkus, senior director of strategic planning for Millennium who tracks obesity research. And many companies are looking to beta3agonists. Beta3agonists are substances that activate receptors involved in thermogenesis, boosting fat-burning. If an effective beta3agonist is found, it could be a kind of "thermostat" or "exercise" pill, Brenkus says.
Obesity treatment research must take endless twists and turns, experts say, because it is clear there's no single cause for obesity.
"There are genetic factors, as well as psychological, environmental, ethnic and behavioral," says Dr. Morton H. Maxwell, UCLA clinical professor of medicine and director of the UCLA University Obesity Center. "You don't know what the mix [of factors] is for each patient. A treatment that works for patient A doesn't always work for patient B."
Then there are societal pressures.
"In our culture, every time two people get together there is either food or drink or both," Maxwell says. "It's hard not to get fat."
Greatly in the '90s
About 97 million U.S. adults are either overweight or obese, according to the National Heart, Lung and Blood Institute of the National Institutes of Health. From 1960 to 1994, the percentage of obese U.S. adults has risen from 13% to 22.5%, and most of the increase has occurred in the 1990s, with frequent restaurant meals and larger portions seen as contributing factors. For some obese people, Xenical might help. Doctors say others will be wary, remembering all too well the withdrawal in 1997 of fenfluramine, the fen part of the popular fen-phen diet combination, after it was linked with heart valve damage.
"There's a general fear of obesity drugs" in the wake of fen-phen, says Dr. Richard Atkinson, an obesity specialist at the University of Wisconsin, Madison, who explains to patients that Xenical works in the gut, not the brain.