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Letter to the editor

Panel: Don't remove diabetes drug

Despite heart risks, Avandia wins support.

By ASSOCIATED PRESS
Published July 31, 2007

The widely used diabetes drug Avandia should remain on the market because its benefits outweigh the risks, but it should carry a strong warning about an increased risk of heart disease, a federal panel said Monday.

The advisory committee concluded that the evidence is suggestive of an increased heart disease risk associated with its use but that the evidence is not sufficiently strong to remove the drug from the market.

The Food and Drug Administration generally follows the recommendations of its advisory panels but is not obligated to do so. The agency's drug office has been split over the Avandia question, leading it to seek the advice of outside experts.

The panel voted 22-1 against recommending Avandia's removal from the market.

The panel said certain groups should not take the drug because their risks are even higher. That includes people taking nitrates, such as nitroglycerin, to ease pain from angina, and those taking insulin for their Type 2 diabetes.

"Physicians will have to think twice before they prescribe the drug for these people," said the panel's chair, Dr. Clifford Rosen of the Maine Center for Osteoporosis.

Both Avandia and another drug in the same family, Actos, carry a warning against use for patients with congestive heart failure, and the FDA recently asked both manufacturers to upgrade that to a so-called black box warning, giving it greater prominence.

The panel did not agree on how strong the new warnings should be.

Dr. Robert Meyer, director of the FDA's Office of Evaluation II, said there was "a fairly unanimous recommendation that came to us," and that the agency would evaluate it carefully in considering labeling changes.

About 21-million Americans have Type 2 diabetes, which most often manifests itself later in life and is associated with obesity. Last year, about 1-million of them took Avandia, which had global sales of $3.4-billion in 2006.

The current uproar about Avandia, whose generic name is rosiglitazone, was triggered by a report in May in the New England Journal of Medicine linking Avandia to a 43 percent increase in myocardial ischemia. Ischemia is an inadequate flow of blood to the heart caused by a partial obstruction of an artery and is often a precursor to a heart attack.

Two other analyses, one conducted by the FDA and one conducted by Avandia's manufacturer, GlaxoSmithKline, yielded similar results, indicating that the drug increases the risk of myocardial ischemia by 30 percent to 40 percent.

The so-called meta-analyses were conducted by combining results from several studies to form a database with a large number of patients. Because of that design, panelists said the results did not conclusively prove cause and effect but merely suggest a possibility that needs to be explored by more directed research.

The panel concluded, however, that the data from other clinical trials was insufficient to rebut the meta-analyses and called on GlaxoSmithKline to conduct more research on the heart issues.

Dr. David Graham, a drug safety officer at the FDA, and Dr. Gerald Dal Pan, director of the FDA's Office of Surveillance and Epidemiology, had asked the panel to call for withdrawal of Avandia.

Graham said 70 percent of diabetics die from heart disease and argued that "any drug that increases the risk of heart disease makes no sense."

He estimated the drug's toxic effects on the heart had caused as many as 205,000 heart attacks and strokes, some of them fatal, between 1999 and 2006. For every month that Avandia is sold, he said, 1,600 to 2,200 patients will suffer more of these events.

He also said Avandia produces no unique benefits compared with other oral diabetes drugs, so there was no reason to keep it on the market.

But other speakers, including patient advocates, said that the drug does have some properties that are different from other drugs. "It is vital to have as many tools in the tool kit as possible," said Raul Fernandes, vice president of the patient advocacy group Mended Hearts.

In their analysis of the risks of Avandia, Graham and Dal Pan relied on a head-to-head comparison of Avandia and Actos, which is manufactured by Takeda Pharmaceuticals. But panel members said that data had not yet been peer-reviewed and had not been presented to them in time for a full evaluation.

Information from the Associated Press and the New York Times was used in this report.

Fast Facts:

What's next

Diabetics can continue taking the diabetes drug Avandia to control their blood sugar, even though the drug likely will receive new government warnings until long-term studies resolve whether it increases the risk of heart attack. About 1-million patients in the United States took Avandia last year.

[Last modified July 30, 2007, 23:04:11]