THIS STORY HAS BEEN FORMATTED FOR EASY PRINTING

New studies add to Avandia concerns

Avandia is a treatment for type 2 diabetes. Avandia is a treatment for type 2 diabetes. (Jb Reed/Bloomberg News)
By Christopher Rowland
Globe Staff / June 29, 2010

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WASHINGTON — Two scientific studies published yesterday reinforced serious health warnings about a heavily marketed diabetes drug, Avandia, made by GlaxoSmithKline PLC.

The studies increase pressure on the Food and Drug Administration as the agency prepares for a meeting July 13 to consider halting a controversial clinical trial and withdrawing the drug from the market.

“We are taking the question of Avandia safety very seriously,’’ Dr. Joshua M. Sharfstein, the FDA’s principal deputy commissioner, said in response to the new studies. He declined to discuss details.

“I don’t want to prejudge the full scientific debate that is going to happen’’ at the July 13 session, he said.

GlaxoSmithKline, a global corporation based in the United Kingdom with US headquarters in Philadelphia, said in a brief statement that its analysis of the accumulating research shows its drug “does not increase the overall risk of heart attack, stroke, or death.’’

Avandia and a competitor drug, Actos, manufactured by Takeda Pharmaceutical Co. of Japan, are prescribed to treat type 2 diabetes, which typically strikes people who are overweight. The treatments work by making the body more sensitive to insulin.

Actos has not been associated with the same negative health effects as Avandia, however, leading to questions about why the FDA should allow Avandia to remain on the market when there is an apparently safer drug that treats the same disease.

One of the two studies released yester day — a review by government researchers of data for 227,000 Medicare patients taking either Avandia or Actos — found that Avandia increased the risk of heart attack, stroke, heart failure, or death by 17 percent. The study was published in JAMA, the Journal of the American Medical Association.

One of the study’s FDA coauthors wrote in an e-mail to agency officials earlier this month that the study indicated Avandia caused an estimated 48,000 additional cardiovascular events among Medicare patients.

“Look at our study, and then ask yourself, ‘Why would you want to take Avandia?’ ’’ coauthor Dr. David Graham, the FDA’s associate director for science and medicine, said in an interview. Graham has urged the agency to force the drug off the market.

The second study was performed by Cleveland Clinic cardiologist Dr. Steven Nissen, who was the first to publish a broad analysis of clinical trials in 2007 that said Avandia raised the risk of heart attack.

Nissen’s findings, published yesterday in the Archives of Internal Medicine, analyze 56 separate clinical trials involving 35,000 patients and confirm his analysis of three years ago. The study found that Avandia elevated the risk of heart attack by 28 to 39 percent.

The growing body of evidence against the drug, and federal regulators’ evolving response to it, is reminiscent of the controversy leading up to Merck & Co.’s withdrawal of the arthritis drug Vioxx in 2004. But a key difference, say specialists, is that Vioxx was taken to control pain across a healthier population. Type 2 diabetes patients are far sicker, so an increase in cardiovascular risk could have a greater impact.

“When you have a drug that increases heart attack by a third in diabetics, it has enormous public health consequences, so it is obviously very concerning,’’ Nissen said.

Nissen has repeatedly called for Avandia’s withdrawal from the market and will be a key scientist testifying at the FDA’s July 13 advisory committee meeting.

In 2008, the agency required GlaxoSmithKline to conduct a clinical trial directly comparing the safety of Avandia and Actos, but it has been slow to recruit patients and critics say it is unethical.

Christopher Rowland can be reached at crowland@globe.com.