Dr. Richard N. Bergman, an expert on obesity and diabetes at the University of Southern California, said the drugs might prove to have serious side effects but, if safe, could become widely used. “It is possible that the couch potato segment of the population might find this to be a good regimen, and of course that is a large number of people.”

The idea of a workout in a pill seems almost too good to be true, but Dr. Evans has impressive research credentials, including winning the Lasker Award, which often presages a Nobel Prize. He is an expert on how hormones work in cells and on a powerful gene-controlling protein called PPAR-delta, which instructs fat cells to burn off fat.

Four years ago he found that PPAR-delta played a different role in muscle. Muscle fibers exist in two main forms. Type 1 fibers have copious numbers of mitochondria, which generate the cell’s energy and are therefore resistant to fatigue. Type 2 fibers have fewer mitochondria and tire easily. Athletes have lots of Type 1 fibers. People with obesity and diabetes have far fewer Type 1 and more Type 2 fibers.

Dr. Evans and his team found that the PPAR-delta protein remodeled the muscle, producing more of the high-endurance Type 1 fiber. They genetically engineered a strain of mice whose muscles produced extra amounts of PPAR-delta. These mice grew more Type 1 fibers and could run twice as far as on a treadmill as ordinary mice before collapsing.

Given that people cannot be engineered in this way, Dr. Evans wondered whether levels of the PPAR-delta protein could be raised by drugs. Pharmaceutical companies have long tried to manipulate PPAR-delta because of its role in fat metabolism, and Dr. Evans found several drugs were available, although they had been tested for different purposes.

In a report in the Friday issue of Cell, he described the two drugs that successfully activate the muscle-remodeling system in mice, generating more high-endurance Type 1 fiber. The drug GW1516 activates the PPAR-delta protein but the mice must also exercise to show increased endurance. It seems that PPAR-delta switches on one set of genes, and exercise another, and both are needed for endurance.

Aicar improves endurance without training. Dr. Evans believes that it both activates the PPAR-delta protein and mimics the effects of exercise, thus switching on both sets of genes needed for the endurance signal.