Amid a salvo of congressional press releases questioning its handling of the diabetes drug Avandia, the Food and Drug Administration issued a “safety alert” Monday, warning the public about the drug’s possible cardiovascular risks.

“Safety data from controlled clinical trials have shown that there is a potentially significant increase in the risk of heart attack and heart-related deaths in patients taking Avandia” for type 2 diabetes,” the agency said.

“Patients who are taking Avandia, especially those who are known to have underlying heart disease or who are at high risk of heart attack, should talk to their doctor about this new information as they evaluate the available treatment options for their type 2 diabetes,” the safety alert advised.

Robert J. Meyer, a senior drug evaluation official at FDA, declined in an afternoon telephone press briefing to offer an estimate of the number of deaths that might be linked to the drug.

“We don’t have a final estimate at this time,” he said. Asked what regulatory action the agency might take, Meyer said “I don’t think I would exclude any regulatory pathway at this point.”

The agency issued the alert the same day the New England Journal of Medicine posted on the Web the results of a study by Cleveland Clinic researchers analyzing 42 studies of the safety effects of the drug, manufactured by GlaxoSmithKline.

The findings suggested that the drug is associated with a risk of heart attack, stroke, and death at least 40 percent higher than in diabetics not taking the drug. The findings “are worrisome because of the high incidence of cardiovascular events in patients with diabetes,” the researchers said. “Because of exposure of such patients to [Avandia] is widespread, the public health impact of an increase in cardiovascular risk could be substantial,” they added.

In an accompanying editorial, the journal said that despite flaws in the study, “in view of the potential cardiovascular risks... the rationale for prescribing [Avandia] is unclear.”Assuming its findings are valid, they indicate “a major failure” of drug monitoring in the U.S., the editorial said.

Meyer indicated that FDA first became aware of a similar analysis submitted to the agency by the company last August, but said that other data from published and unpublished trials provides “contradictory evidence about the risks in patients treated with Avandia.”

Because the drug’s labeling already contains information indicating an increased cardiovascular risk with the drug, and because of the contradictory evidence, the agency hasn’t yet changed Avandia’s labeling to reflect the company’s analysis, he said.

House Democrats said they would investigate. FDA “ has known about this problem for at least eight months and perhaps even longer,” said House Energy and Commerce Committee Chairman John Dingell (D-Mich.) in a press release Monday.

“What we don’t know is why diabetics and their doctors haven’t been notified of the substantial risk to the heart,” he said. “FDA’s apparently callous disregard for the safety of diabetics taking Avandia is very reminiscent of the agency’s failure to move on Vioxx when substantial safety signals first became known,” added Rep. Bart Stupak, D-Mich.

House Government Reform Committee Chairman Henry Waxman, D-Calif., announced Monday that he will chair a hearing June 6 on FDA’s handling of Avandia. And Senate Finance Committee Chairman Max Baucus, D-Mont., and Ranking Member Charles E. Grassley, R-Iowa, announced Monday that they have written to FDA to ask what agency officials knew about Avandia and when they first learned it.

GlaxoSmithKline issued a statement Monday saying it "strongly disagrees" with the findings of the New England Journal study. The study is "based on incomplete evidence and a methodology that the author admits has significant limitations," the company said. A more rigorous way of evaluating the safety of the drug is to monitor its effects in large scale, long-term clinical trials, it added. Results from those trials either show it has comparable risks to similar drugs or that the increased cardiovascular risk it poses is based on too few "events" on which to base sound conclusions. The company said it "stands firmly behind the safety of Avandia when used appropriately."