GSK - Avorn on Avandia

The (FDA) agency is now addressing yet another follow-on drug as the glitazone story evolves. In 1997, the first entry in this class of antidiabetic agents, troglitazone (Rezulin, Parke-Davis), was observed to cause fulminant hepatic necrosis, sometimes fatal. Regulatory authorities throughout the world quickly concluded that the product had an indefensible risk–benefit ratio, and it was withdrawn from the market, often within just a few months of approval.

Yet the FDA and its advisory committee were swayed by the arguments of the manufacturer and kept it in use in the United States for 2 years after it had been made unavailable in nearly every other country.4

Now, a decade later, troglitazone's younger sibling, rosiglitazone (Avandia, GlaxoSmithKline), has been implicated in raising the risks of congestive heart failure and myocardial infarction, without impressive evidence of a countervailing advantage in clinical outcomes.

An advisory committee meeting on July 30, 2007, did not fuel hopes for a new era of data-driven reform.

The committee voted, 20 to 3, that rosiglitazone increases cardiac ischemic risk in type 2 diabetes but then recommended, by a 22-to-1 vote, that the drug remain in use. The decision was more suggestive of Rezulin redux (and of Redux) than it was of resolve. Although Avandia has been prescribed widely since 1999, several participants noted that neither the manufacturer nor the FDA had carried out enough safety studies to permit a clear conclusion.

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