Editor's Notes:

This article, from the Wall Street Journal, reports that Avandia's class of drugs, called peroxisome proliferated–activated receptors or PPARS, have a long track record of both extraordinary promise and safety problems. Companies are working hard to maximize the benefit of PPAR drugs while minimizing the risks; hopefully, the backlash against Avandia will not shelve promising research in this area.

"It is a challenging class of drugs," said Robert Meyer, who heads the Food and Drug Administration office that oversees diabetes medications. "These are drugs with many effects and many targets" in the body.

On Monday, the New England Journal of Medicine released an analysis by Cleveland Clinic cardiologist Steven Nissen linking Avandia to a potential risk of heart attacks. Glaxo has said it disagrees with the finding, which it says is contradicted by data from sources the company considers stronger. But analysts warned yesterday that concerns about safety could cut Avandia's sales in half.

The PPAR drugs can target three different receptors in the cell nucleus. Avandia and Actos, which affect the PPAR-gamma receptor, can bring down blood sugar and are used to treat diabetes. A sister class called PPAR-alpha medicines, which includes older drugs such as gemfibrozil and fenofibrate, tends to boost HDL, or "good," cholesterol, and reduce triglycerides, or fats in the blood. A third type, PPAR–delta drugs, are seen as a prospective treatment for obesity. The jackpot would be medications that combine more than one of these mechanisms.

The drugs also may hold potential in other areas. Glaxo is studying Avandia for Alzheimer's disease. Bruce Spiegelman, a professor of cell biology at Harvard Medical School, plans to examine a PPAR-gamma medication for cancer, after "extremely good" data in animals. "You have the potential to affect a lot of things, and that can be good and that can be bad," he says of the PPAR drugs.

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A Glaxo spokeswoman said the British company is studying new PPAR drugs in early-stage development. She said it was difficult to say whether such drugs are especially cursed with side effects. "Are there side effects in the PPAR class? Yes. Compared to the conditions that diabetes can lead to—blindness, kidney failure and amputation—we think the risk–benefit profile [of Avandia] is a very positive one."