Now doctors are back to square one, with precious few medicinal options for the two thirds of Americans who are overweight. For the one third who are obese, the situation is dire. Obesity, defined as having a body-mass index of 30 or greater, sets the stage for diabetes and killer conditions such as heart disease, stroke and cancer. Aside from advice (stop eating) and stomach surgery for the severely obese (say, 5-foot-8, 265 pounds), there are just two anti-obesity medications approved for long-term use, and the pounds come right back on as soon as you stop taking them. The appetite suppressant sibutramine, a non-addicting cousin of amphetamines, can increase blood pressure in an already hypertensive population, and the fat blocker orlistat (sold over the counter as Alli) can cause what doctors call "fecal urgency" and diarrhea. Worse, both produce only marginal weight loss. "That's the real killer," says Steve Bloom, who heads the metabolic-medicine department at Imperial College London. "The reality is, we seem to be getting nowhere."