Warning on diabetes drug could be a replay of Vioxx

Washington -- A New England Journal of Medicine article prompted the Food and Drug Administration to issue a safety alert for Avandia, or rosiglitazone, a drug used by several million patients to treat type 2 diabetes. Safety data from clinical trials indicated that the drug poses a possible increase in the risk of heart attacks, according to the article, which was published online May 21.

Not only did the article prompt the need for physicians to look more closely at who is prescribed the drug, but it also raised alarms anew over the FDA's ability to carry out effectively its role as safety monitor for the nation's drug supply.

The warning was posted by Steven Nissen, MD, chair of the Cleveland Clinic's Dept. of Cardiovascular Medicine, who analyzed 42 trials of rosiglitazone, which was approved by the FDA in 1999. Dr. Nissen and Cleveland Clinic statistician Kathy Wolski, MPH, found that the use of the drug was associated with an increased risk of heart attack and cardiovascular death -- by 43% and 64% respectively -- compared with placebo.

The findings represent a particular health concern, Dr. Nissen said, because more than 65% of deaths in diabetic patients are attributed to heart disease.

Drugmaker questions findings

The drug's manufacturer, GlaxoSmithKline, strongly disagreed with the researchers' conclusions.

The firm charged that the findings were based on incomplete evidence and questionable methodology. An ongoing clinical trial on the drug has been designed to look at cardiovascular outcomes, according to a statement that has been released by the company. And, so far, the independent monitoring boards responsible for overseeing the trial's safety have not found any risks that would require halting the trial, noted the Glaxo statement.

The findings prompted an editorial, also published online May 21 by the NEJM, urging Congress to pass tougher legislation that requires the FDA to scrutinize a drug throughout its life span.

Although the Senate recently passed a drug safety bill, its provisions would not necessarily have identified the cardiovascular risks detected in Dr. Nissen's review, said the editorial's authors Bruce Psaty, MD, PhD, professor of medicine, epidemiology and health services at the University of Washington, and Curt Furberg, MD, PhD, professor of public health sciences at Wake Forest University School of Medicine in North Carolina.

"The public would benefit from additional revisions to the drug-safety legislation as it moves through the House of Representatives," Drs. Psaty and Furberg wrote.

The FDA is now weighing the data on rosiglitazone, said Steven Galson, MD, MPH, director of the FDA's Center for Drug Evaluation and Research.

"We will complete our analysis and make the results available as soon as possible," Dr. Calson said in a statement. "The FDA will take the issue of cardiovascular risk associated with Avandia and other drugs in this class to an advisory committee as soon as one can be convened."

Meanwhile the FDA is asking that physicians considering rosiglitazone for their patients review the warnings for cardiac adverse events included in the prescribing information.