U.S. health regulators dealt a major blow to the controversial diabetes pill Avandia Thursday, requiring doctors and patients to sign consent forms before starting a prescription of the drug. At the same time, European regulators ordered it off the market. The split decision underscores lingering safety questions about a once-blockbuster drug taken by millions of patients over the last decade.
Here are some key events in the drug's history.
_May 1999: The Food and Drug Administration approves GlaxoSmithKline's drug Avandia based on studies showing it helps control blood sugar levels.
_June 2003: GlaxoSmithKline publishes study results claiming that Avandia has benefits for the heart.
_May 2007: Dr. Steven Nissen of the Cleveland Clinic publishes medical journal article estimating that patients taking Avandia were 43 percent more likely to experience heart attack than those taking other diabetes drugs or no diabetes medication.
_July 2007: A panel of FDA advisers votes 22-1 against recommending removing Avandia from the market, saying evidence the widely used drug was risky to the heart wasn't conclusive enough to merit such drastic action.
_November 2007: The FDA adds an unusual warning label to Avandia saying that the evidence is "inconclusive" on whether the drug increases heart attack risk.
_February 2010: A report by the Senate Finance Committee concludes that GlaxoSmithKline had full knowledge of the heart risks of its drug in late 2004 or early 2005. The report prompts a new round of scrutiny of Avandia's safety.
_June 2010: FDA scientist Dr. David Graham publishes a paper estimating Avandia has caused as many as 100,000 heart attacks, strokes, deaths and cases of heart failure in the U.S. He urges the FDA to withdraw the drug.
_July 2010: A 33-member panel of FDA experts votes 20-12 to keep Avandia available in the U.S. Of the 20 who voted to keep it on the market, half say it should only be available on a limited basis.
_Sept. 23, 2010: FDA announces major restrictions on which patients can get Avandia, while European regulators order it off the market. Both decisions were based on heart attack risks.