Diabetes Drug Avandia to Get Strictest Warning About Heart Risk

By Anastacia Mott Austin

Congress wants to know why the FDA waited more than a year to require GlaxoSmithKline to have a label warning of heart risks to patients taking the diabetes drug Avandia.

Amid the investigation by the U.S. Congress, FDA Commissioner Andrew von Eschenbach announced that the agency would now require the "black box" label, the most serious health warning that can be placed on a drug, for Avandia (and a similar drug made by Eli Lilly, Aptos), because "despite existing warnings, these drugs were being prescribed to patients with significant heart failure." The announcement was made at a crowded hearing in Congress Wednesday.

Some health experts claim they tried to warn GlaxoSmithKline almost eight years ago that the drug had potential to cause heart problems. Dr. John Buse, soon to be the new president of the American Diabetes Association, was an endocrinologist at the University of North Carolina School of Medicine in 1999 when he tried to make public his concerns about the drug.

He says he was threatened by the pharmaceutical company, who telephoned him and told him he might be sued for his comments. "During those calls, it was mentioned on two occasions that there were some in the company who felt that my actions were scurrilous enough to attempt to hold me liable for a loss in market capitalization," he told reporters. He added, "I was characterized as a liar."

Dr. Buse shared a letter he’d written to GlaxoSmithKline in 1999, in which he asked the drug company to stop its threats against him. He wrote, "Please call off the dogs. I cannot remain civilized much longer under this kind of heat."

Buse also sent a letter to the FDA about his fears of the drug. In a statement read to Congress, a representative of GlaxoSmithKline responded to Buse. "We regret if, at any time, Dr. Buse felt the conduct of any employee was contrary to the spirit of open, scientific debate."

In addition, an expert on drug safety from the FDA itself tried to have the warning label added to the drug last year but was rebuked by the agency. Dr. Rosemary Johann-Liang told reporters that she had recommended a "black-box" label for Avandia, citing concerns for heart problems, but that the FDA gave her a reprimand instead.

Congress wants to know why.

The hearing Wednesday was called by U.S. Representative Henry Waxman (D-Calif), after a recent report by the New England Journal of Medicine reported that Avandia could potentially raise heart attack risk by 40 percent.

Waxman had harsh words for the FDA. During the hearing, he said, "Despite additional warnings from outside experts, despite the millions of patients who rely on Avandia to control their blood sugar, and despite the potential risks involved, [the] FDA never required the manufacturer to conduct a thorough post-market study of its heart risks."

Representative Stephen Lynch (D-Mass) asked the FDA witnesses to see if they could easily locate the existing warning for heart risk on the Avandia label. Von Eschenbach could not locate the information, and finally asked another FDA witness, Dr. John Jenkins, for help. Dr. Jenkins did locate the information on a small section in the label packet. Von Eschenbach then stated the agency was currently in the process of making its drug labels more readable.

The chairman for research and development at GlaxoSmithKline, Dr. Moncef Slaoui, stated that the drug company stands behind its product. "[We] strongly believe that the overall safety of Avandia is comparable to other available oral anti-diabetes medicines."

Added Chris Viehbacher, the president of GlaxoSmithKline in the United States, "It wasn’t our understanding that [the FDA] had come to a final conclusion on this issue [of the label], but if they have then obviously we’ll make the change."