A review by federal health scientists reinforces potential ties between the diabetes pill Avandia and heart attack and death, opening the door for government action, including a possible withdrawal of the once blockbuster drug.

The Food and Drug Administration posted an exhaustive 700-page review of the GlaxoSmithKline drug online Friday ahead of a meeting next week to review the safety of Avandia, which is used by hundreds of thousands of diabetics in the U.S.

FDA scientists reviewed dozens of studies of Avandia, including one which Glaxo has pointed to as proof of the drug's safety. But an FDA reviewer said the study was plagued by "serious flaws" and actually supports the case against Avandia.

The FDA holds a special two-day meeting starting Tuesday to help decide what course of action to take. A panel of outside expert physicians will vote on a range of recommendations for Avandia including:

— Adding additional warning labels

— Limiting which doctors can prescribe the drug

— Pulling the drug from the market

The FDA is not required to follow the advice of its outside panels, though it usually does.

Part of the reason the FDA is seeking outside advice is because of disagreements among its own scientists.

"There's not complete unanimity within the FDA about the interpretation of these data, and that's one of the reasons we're going to the advisory committee," said Dr. Janet Woodcock, head of the FDA's drug center.

The European agency that evaluates medicine also said Friday it will review Avandia one week after the FDA's panel meets.

Avandia was Glaxo's third best-selling drug in 2006 with U.S. revenue of $2.2 billion, according to health care statistics firm IMS Health. But safety concerns swirling around the drug have pummeled sales since 2007, with sales falling 75 percent to $520 million last year.

In 2007 an analysis of dozens of studies first linked the drug to heart attacks. The FDA responded by adding a warning label to the drug later that year.

But new data on Avandia's risks and pressure from Capitol Hill have prompted the agency to re-examine the drug's safety.

Avandia is still used by hundreds of thousands of Americans with type 2 diabetes to control blood sugar levels. The drug works by increasing the body's sensitivity to insulin, a key protein needed for digestion.

Critics of Avandia, including a high-profile FDA scientist, argue there are safer alternatives.

Last month a medical journal published an analysis suggesting Avandia is more likely to cause strokes and heart-related death than a rival drug, Actos. Actos is made by Japan-based Takeda Pharmaceuticals and has gobbled up 70 percent of the market for diabetes drugs in Avandia's class.

The paper's author Dr. David Graham, the FDA scientist who wants the pill banned, estimated as many as 100,000 heart-related adverse events may have been caused by Avandia.

Graham and several colleagues analyzed medical records of more than 225,000 elderly Medicare patients.

A key question at next week's meeting will be how much weight to give analyses like Graham's, which pool information from massive datasets.

London-based Glaxo has argued for years that Avandia's safety should only be assessed based on clinical trials, which are considered the gold standard of medical research. The studies enroll similar groups of patients who are given one of two pills and followed over time to see how patients fare.

"Our position is that if you look at the randomized clinical trials, all of them do not show evidence of cardiovascular harm," said Dr. Jai Patel, vice president of cardiovascular development at GlaxoSmithKline.

For more than a year the company has pointed to a study called RECORD which showed no heart problems in patients taking Avandia.

But according to the FDA's review, "RECORD was inadequately designed and conducted to provide any reassurance" about the heart safety of Avandia.

Questions about what Glaxo knew about its drug and when will hang over next week's deliberations. In February a Senate investigation concluded the company knew about safety risks with the drug in 2005 — two years before they were publicized. Senate investigators also faulted the FDA for not making the issue public sooner.

Lawmakers on Capitol Hill have already painted Avandia as a test of the agency's enforcement stance, similar to Vioxx. Vioxx was a blockbuster painkiller from Merck which was withdrawn in 2004 after showing links to heart attack and stroke. Critics said lives could have been saved if the FDA had acted more swiftly.

But some experts reject the comparison between the two drugs.

Parsing Avandia's risks is more challenging than with Vioxx because diabetics are already at increased risk for heart problems, according to UBS analyst Gbola Amusa.

He points out that many top lawyers — including some who successfully sued Merck over Vioxx — have already settled with GlaxoSmithKline, suggesting they didn't have enough evidence to take Glaxo to court.

"To show that Avandia was the proximate cause of these heart attacks would be exceptionally difficult," said Amusa, who is trained as a physician.