By Rob Stein
Washington Post Staff Writer
Tuesday, June 29, 2010; A02
Two teams of researchers have produced powerful new evidence that the diabetes drug Avandia increases the risk of heart problems and strokes, renewing questions about the safety of the medication.
One analysis, involving more than 35,500 people, found that Avandia significantly raises the chances of a heart attack. The second, a federal analysis of more than 227,500 Medicare patients -- the largest such study to date -- found that the drug boosts the risk for strokes, heart failure and death.
The new research, released Monday, should prompt the Food and Drug Administration to remove the drug from the market, according to the researchers who led the analyses and several drug-safety advocates.
"There's no reason to keep this drug on the market," said Steven E. Nissen, a Cleveland Clinic cardiologist who conducted one of the analyses and has long criticized the drug. "This is a harmful drug."
In a statement, GlaxoSmithKline, which makes Avandia, stood by the medication, saying many other, more reliable studies have found no evidence the drug is unsafe. The studies that found no risk were better designed and therefore more reliable, the company says.
"Taken together, these trials show that Avandia does not increase the overall risk of heart attack, stroke or death," the company said in a statement.
A Senate investigation released earlier this year concluded that GlaxoSmithKline knew about the possible risks of Avandia for years but failed to sufficiently warn the FDA and consumers.
The new data will be considered next month at special joint meeting of two FDA advisory panels to reevaluate Avandia's status, an agency official said.
"These are very important papers and will contribute to our evaluation of the safety of this medication," said Joshua M. Sharfstein, the agency's principal deputy commissioner.
Avandia had once been one of the world's most popular drugs, with sales exceeding $3 billion annually. The drug was approved in 1999. It treats Type 2 diabetes, the most common form of the disease, by sensitizing the body to insulin, controlling blood sugar levels. It was considered widely effective. But a series of studies have raised questions about whether it raises the risk for cardiovascular problems, a leading cause of death among diabetics. That prompted the FDA to issue a warning about the drug's safety, causing sales to plummet, but the agency decided in 2007 against removing it from the market.
Coming on the heels of safety concerns about the blockbuster painkiller Vioxx and other prescription medications, as well as a series of high-profile food safety cases, questions about Avandia have fueled criticism that the FDA is lax in regulating the food and drug industries.
"I'm hoping with a new administration and new leadership they will act differently," Nissen said. "This is a defining moment for the new administration."
But David J. Graham of the FDA's Center for Drug Evaluation and Research said he doubted the agency would pull the drug. A longtime critic of Avandia and the FDA's drug safety record, he conducted the second new analysis.
"FDA, unfortunately, has not changed," Graham said. "It has not improved its approach to drug safety. It does not value drug safety."
Sharfstein, however, defended the FDA, saying the agency wanted to examine the latest data before making a decision. "FDA is committed to making decisions about Avandia based on all the best available science," he said.
In one of the new analyses, Nissen and a colleague pooled data from 56 studies involving 35,531 people, including 19,509 who took Avandia. In a paper released online by the Archives of Internal Medicine, the researchers concluded that the drug increased the risk for heart attacks from 28 percent to 39 percent. The pair calculated that the drug would cause one heart attack among every 37 to 52 people who used it for five years.
In the second analysis, Graham and his colleagues analyzed Medicare records for 227,571 people who took either Avandia or another diabetes drug called Actos from 2006 to 2009.
They found that those who took Avandia were 27 percent more likely to have a stroke, 25 percent more likely to develop heart failure and 14 percent more likely to die during the study period than were those who took Actos. Based on the findings, released online by the Journal of the American Medical Association, the researchers estimated that there would be one heart attack, death, stroke or heart failure in every 60 people who took the drug for one year.