A new analysis in The New England Journal of Medicine finds the type 2 diabetes med “significantly increases” the risk of heart attacks. The drug was also associated with an increased risk of death from cardiovascular causes that had “borderline significance.”

The analysis, which was conducted by Steve Nissen, a cardiologist at the Cleveland Clinic, reviewed 42 pooled studies and was posted earlier on the New England Journal of Medicine’s Web site. The news sent Glaxo stock diving by more than 6 percent at midday.

In a conference call, Glaxo’s chief of diabetes drug development, Lawson McCartney, insisted the analysis is not definitive scientific proof. The drugmaker, which strongly disagrees with the analysis, isn’t seeing “anything like” the risks reported, the Associated Press writes. “We remain very confident in the safety and of course in the efficacy of Avandia as an important diabetic medicine.”

The analysis found that patients on Avandia had a 43 percent greater risk of having a heart attack compared to patients not receiving the drug. The trials involved 15,560 patients who received drugs containing rosiglitazone, the main ingredient in Avandia, and 12,283 who either received other drugs or a placebo.

In an accompanying editorial, Bruce Psaty of the University of Washington and Curt Furbert of Wake Forest University wrote: “In view of the potential cardiovascular risks and in the absence of evidence of other health advantages, except for laboratory measures of glycemic control, the rationale for prescribing rosiglitazone at this time is unclear. Unless new data provide a different picture of the risk–benefit profile, regulatory action by the FDA is now warranted…”

“…Ongoing trials using rosiglitazone may provide important new data, but for a drug approved in 1999, the delay in obtaining information about health outcomes has already been considerable. During the market life of rosiglitazone, tens of millions of prescriptions for the drug have been written for patients with type 2 diabetes. Insofar as the findings of Nissen and Wolski represent a valid estimate of the risk of cardiovascular events, rosiglitazone represents a major failure of the drug-use and drug-approval processes in the United States.”

Robert Meyer, head of the FDA office that reviews diabetes drugs, says other data contradicted those findings. “FDA has not confirmed the clinical significance of the reported increased risk in the context of other studies,” Meyer told reporters during a conference call, writes Reuters.

In a statement, John Dingell, the Michigan Democrat who chairs the House Committee on Energy and Commerce, and Bart Stupak, another Michigan Democrat, who chairs the Subcommittee on Oversight and Investigations, pledge to investigate Glaxo and the FDA.

“We learned from an FDA briefing that the agency has known about this problem for at least eight months and perhaps even longer,” said Dingell. “What we don’t know is why diabetics and their doctors haven’t been notified of the substantial risk to the heart from a drug prescribed to protect the cardiovascular system.”

“It is incredible that the agency charged with protecting the public health has such a poor record when it comes to post market drug safety,” said Dingell. “Regrettably it is incidents like this that demand legislative changes in the way FDA deals with drug safety. The Committee will address these dangerous shortcomings while writing legislation to reauthorize PDUFA.”

Said Stupak: “Like Vioxx, Avandia may have unnecessarily risked the lives of tens of thousands of Americans.”

An in an e-mail, a spokeswoman for Henry Waxman, the California Democrat who chairs the House Committee on Oversight and Government Reform, wrote that he plans to hold a hearing into the FDA’s role in “evaluating the safety” of Avandia.

Further reading:
The NEJM study;
The NEJM editorial;
Glaxo’s complete statement.

[tags]Avandia, Cleveland Clinic Foundation, GlaxoSmithKline, Steve Nissen[/tags]