The High Cost of the Diabetes Controversy

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"People heard 43% and they think it is a very big number, but if you look at the actual number of heart attacks on Avandia it's an increase of only 0.1% in absolute risk," says Dr. Sue Kirkman, vice-president for clinical affairs at the American Diabetes Assn.

Nissen also charges that there is no proof that Avandia has any benefit beyond controlling blood sugar levels and says that many other drugs are available for that purpose. But to endocrinologists, such control is critically important to avoid the many complications of diabetes, such as foot ulcers and heart disease, and they want as many drugs in their arsenal as possible in case a patient is resistant to one. "It is well established that lowering blood sugar makes a huge difference in outcomes for diabetics," says Dr. Robert Rushakoff, a professor at the University of California at San Francisco's endocrinology department. "If I have a patient who is on the drug and they are doing well, I am not going to take them off." Dr. Samuel Andrews, director of the clinical diabetes center at Ochsner Health System in New Orleans, says the meta-analysis is not a true scientific study. "I don't use a lot of Avandia because it can cause weight gain, but it does have value in some patients. I think it would be premature to take it off the market."

Glaxo Awaits New Study

Nissen dismisses such criticism as self-serving. "The diabetes specialists have a very big problem with cognitive dissonance," he says, in that they have to justify why they have been prescribing Avandia. "A cardiologist tells them this drug is dangerous, and no doubt that there is some pushback. But I believe the results we have reported will stand the test of time."

Nissen points out that Glaxo, in its own meta-analysis, found a 30% increase in the risk of heart attack from Avandia and reported those results to the Food & Drug Administration last August. The agency, however, decided there was too much conflicting data to take action. Although it did issue a safety alert on Avandia after the report was published in the NEJM, FDA officials have no plans to withdraw the drug. They want to wait for the results of a 4,400-patient, eight-year clinical trial called RECORD, which is designed to look for cardiovascular outcomes in Avandia. Those results won't be out until 2009, and Nissen says that's too long to wait: "If we are right and there is a 43% increase, then waiting for results of the RECORD trial to warn people is just not acceptable."

But Glaxo, which is vigorously defending its $3 billion a year drug, says an independent board's interim analysis of the trial found no signs that safety concerns warrant halting production. It also says a database of some 30,000 patients revealed no increased risk of heart attack. British medical journal The Lancet has also urged caution in interpreting the results of Nissen's meta-analysis.

Behind all this back-and-forth is a larger issue about how the FDA regulates drugs. Senator Chuck Grassley (R-Iowa) has already scheduled congressional hearings for June 6 to investigate why the FDA did not take a tougher stand on Avandia, and observers expect the agency to be far more cautious, at least for the near term. Then there are those doctors who deal every day with diabetes, one of the nation's biggest killers. "It's easy for an academic or a politician to sit on a soapbox and make declarations about this drug because they have an axe to grind, but I don't think that is doing the patient any good," says Lamberts, of Evans Medical Group.

Arnst is a senior writer for BusinessWeek based in New York.