More than 6 million people worldwide have taken the drug sold by London-based GlaxoSmithKline PLC since it came on the market eight years ago. Pooled results of dozens of studies revealed a 43 percent higher risk of heart attack and a 64 percent greater risk of cardiovascular death, according to the review published by the New England Journal of Medicine.
Experts said the overall risk was small and cautioned people not to stop taking the drug on their own but to talk to their doctors.
"There are more heart attacks, more strokes, deaths, et cetera," one of the study's researchers, Dr. Steven Nissen, said. "It is most urgent that both the FDA and the company look at the original source data and do careful analysis."
The company downplayed the report of heart risks, saying the analysis by Dr. Nissen and statistician Kathy Wolski at the Cleveland Clinic is not definitive scientific proof. In a conference call Monday, Dr. Lawson McCartney, who leads Glaxo's diabetes drug development, said the company is not seeing "anything like" the problems reported in the medical journal.Only On The Web: Study author Dr. Steven Nissen discusses the link between Avandia and increased risk of heart attack and cardiovascular death.
"We remain very confident in the safety and of course in the efficacy of Avandia as an important diabetic medicine," McCartney said.
GlaxoSmithKline earns $3 billion a year from the drug, the biggest-selling diabetes drug in the world, according to Forbes magazine.
The government will take no immediate action on a label change or other measures regarding the drug, said Dr. Robert J. Meyer of the U.S. Food and Drug Administration's Center for Drug Evaluation and Research.
FDA officials acknowledged that Glaxo submitted information last August indicating some increased risk from the drug but that other studies were contradictory.
CBS News correspondent Wyatt Andrews reports the FDA said it has studied the same data as Nissen, but that "unpublished data" suggests "contradictory evidence about (Avandia's) risks" — which essentially means the FDA doesn't have enough evidence to pull the drug off the market.
However, several members of Congress expressed alarm at the report and said they would hold hearings on the safety issues.
Avandia is used to treat Type 2 diabetes, the most common form of the disease, which is linked to obesity and afflicts 18 million Americans and 200 million people worldwide. This form of diabetes occurs when the body does not make enough insulin or cannot effectively use what it manages to produce. Avandia helps sensitize the body to insulin and was considered a breakthrough medication for blood-sugar control.
In a strongly worded editorial accompanying the study, patients were warned not to quit Avandia on their own without discussing their concerns with their doctors, wrote Drs. Bruce Psaty and Curt Furberg. To the extent that the new analysis shows valid risks, the drug "represents a major failure of the drug-use and drug-approval processes in the United States," they said.
Psaty, a researcher at the University of Washington, said the Nissen study means there's no good reason for most patients to take Avandia.
"There is little evidence for using this drug," Psaty told WebMD. "The purpose of reducing blood sugar is to prevent cardiovascular events. Now the possibility of cardiovascular benefit associated with Avandia appears remote — indeed, it appears linked to harm. So the rationale for prescribing it at this time is just not clear."
When the drug was approved, "evidence was at best mixed" on its benefit, wrote the two doctors. Both have been frequent critics of the FDA's failure to spot dangers in the drug approval process and its conduct in the case involving Vioxx. The popular arthritis medicine sold by Merck & Co. was taken off the market in 2004 when heart problems came to light after it had been taken by millions of people
Several experts said Avandia was another example of the FDA failing to detect a safety problem early enough.
"This study is sure to increase criticism of the U.S. Food and Drug Administration for approving Avandia in the first place," said CBS News correspondent Barry Bagnato.
The report on the diabetes drug's risks follow Glaxo's $2.5 million settlement of a lawsuit filed by former New York Attorney General Eliot Spitzer over the release of data on the safety and effectiveness of its drugs. Spitzer, now New York governor, accused Glaxo of fraudulently withholding some results of studies that had examined the safety of prescribing the antidepressant Paxil to children.
GlaxoSmithKline disputed that it attempted to mislead anyone, and said it has always been in favor of widespread disclosure of clinical trial results.
The company's clinical trials registry (http://ctr.gsk.co.uk) is available to the public, although the reports within it are highly technical and may appear incomprehensible to an untrained reader.
In a study published last September, the drug rosiglitazone (Avandia) appeared to cut the risk of developing diabetes or dying by more than half. It also helped restore normal blood-sugar function in many participants. That study involved about 5,000 people with "pre-diabetes," or blood-sugar abnormalities.
But even that study's researchers acknowledged that a small percentage of those on Avandia developed heart failure.