America's Obesity Crisis:Pills in the Pipeline

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On the other end of the spectrum are therapies that aim directly at fat tissue. Scientists at M.D. Anderson Cancer Center in Houston are trying to starve fat cells by attacking proteins embedded in the blood vessels that feed those cells. In experiments on obese mice, their excess fat melted away in a matter of weeks. Not only did this strategy eliminate fat tissue--the animals lost 30% of their body weight--but mice that were dangerously overweight quickly regained their health. In fact, early signs of diabetes reversed, fat no longer accumulated in the liver, and cholesterol and glucose levels dropped to normal. "We don't know if this will happen in people," warns Dr. Wadih Arap, a co-leader of the study. "But conceptually, it's possible."

Even more exciting is a compound that appears to attack obesity through both the brain and the gut. Called rimonabant, and developed by Paris-based Sanofi, it is entering the final stages of human testing. Like Axokine and leptin, rimonabant was designed to make the body feel full. But scientists were pleasantly surprised to find that it also lowered triglyceride levels 15% and raised good cholesterol 22%--far more than would have been expected from weight loss alone. There is also evidence that patients on rimonabant may become more sensitive to the action of insulin, which can halt the progression from prediabetes to diabetes. "In addition to reducing food intake, rimonabant may have an effect on fat cells themselves," says Dr. Jean-Pierre Despres of Laval University in Montreal, who is leading one of the drug's clinical trials. "That's clearly exciting."

Whatever form the new drugs for obesity may take, one thing is clear: the most effective treatments will probably involve a mix of agents chosen to match each patient's needs. "A few years ago, we were all looking for a single magical cure for all obesity," says Dr. George Yancopoulos, chief scientific officer of Regeneron. Now the answer seems more likely to come, as weight loss usually does, one hard-fought-for step at a time.