Two teams of researchers have produced powerful new evidence that the diabetes drug Avandia increases the risk for heart problems and strokes, renewing questions about the safety of the medication.
One analysis, involving more than 35,500 patients, found 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 the drug boosts the risk for strokes, heart failure and death.
Taken together, 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. "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.
The American Heart Association issued a statement reminding patients not to stop taking any medicine without talking with their doctors first. The new study is not definitive enough to prove harm but "deserves serious consideration" and should be discussed between patients and their doctors, the statement says.
Some experts say more research is needed and are weary of what they call drug politics, according to a report in USAToday. Drugs like Avandia "are important agents in the management of diabetes," the paper quoted Joel Zonszein, professor of clinical medicine at Montefiore Medical Center in the Bronx as saying. "Avandia is already rarely prescribed. Let the free markets work following science, not politics."
The new data will be considered next month at special joint meeting of two FDA advisory panels to re-evaluate 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 most popular drugs in the world, 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 increases the risk for cardiovascular problems, which is one of the leading causes 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 too lax in regulating the food and drug industries.
"I'm hoping with a new administration and new leadership they will act differently. This is a defining moment for the new administration," Nissen said.
But David Graham, a longtime critic of Avandia and the FDA's drug safety record who conducted the second new analysis, said he doubted the agency would pull the drug.
"FDA, unfortunately, has not changed. It has not improved its approach to drug safety. It does not value drug safety," said Graham, who heads the FDA's Center for Drug Evaluation and Research.
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.
(Optional Add End) In one of the new analysis, Nissen and a colleague pooled data from 56 studies involving 35,531 patients, including 19,509 who took Avandia. In a paper released online by the Archives of Internal Medicine, the researchers concluded 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 patients who used it for five years.
In the second analysis, Graham and colleagues analyzed Medicare records for 227,571 patients who took either Avandia or another diabetes drug called Actos from 2006 to 2009.
In a paper released online by the Journal of the American Medical Association, the researchers found those who took Avandia were 27 percent more likely to suffer a stroke, 25 percent more likely to develop heart failure and 14 percent more likely to die compared with those who took Actos. Based on the findings, the researchers estimate that there would be one heart attack, death, stroke or heart failure in every 60 patients who took the drug for one year.