We wrote about the safety issues relating to Avandia in the June issue. It now appears that GlaxoSmithKline Plc was actually warned by regulators in 2001 against playing down the risk of cardiac disease associated with the diabetes drug. A year earlier, in March 2000, Dr. John Buse, a diabetes expert from the University of North Carolina, Chapel Hill, wrote a letter to the federal Food and Drug Administration (FDA) complaining about the company’s “rampant abuse of clinical trial data” related to the drug’s cardiovascular safety. The two letters, along with the concerns voiced by the company’s own advisers, are good evidence of early concerns about Avandia’s impact on the heart. Dr. Buse recently testified in Congress that Glaxo threatened to sue him because he spoke out about Avandia.

In February 2001, the company agreed to change Avandia’s warning label to show that studies found an increased risk of heart problems for patients taking the drug in combination with insulin. In July 2001, the FDA warned Glaxo in a letter that its marketers should stop denying or minimizing that patients taking the drug with insulin had an increased risk of “heart failure or other cardiovascular adverse events.” Regulators criticized Glaxo for continuing to “engage in false or misleading promotion of Avandia.” The FDA sent five warning letters to Glaxo in a two-year period starting in 1999 over the company’s advertising and marketing of the diabetes drug. Glaxo never admitted any connection between Avandia and increased risk of heart attacks.

The recent Cleveland Clinic meta-analysis found Avandia users were 43% more likely to have a heart attack. The cardiologists at the Cleveland Clinic were concerned for diabetic patients who are already at a higher risk of heart attack. The Cleveland Clinic study was done by Dr. Steven Nissen, a heart researcher who also was among the first to blow the whistle on Merck & Co.’s Vioxx. Our firm is currently looking over a number of potential claims, but we have established a strict set of standards for taking Avandia cases. Only claims that meet the criteria will be investigated.