Endocrine Insider
August 1, 2007

In a public hearing held on July 30, 2007, a joint panel of the Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted 22-1 to recommend to the U.S. Food and Drug Administration (FDA) that the diabetes drug Avandia (rosiglitazone) be kept on the market with the addition of a black box warning for specific subgroups of patients. After a number of presentations by GlaxoSmithKline (GSK) and the FDA on further analysis of the data related to the potential increased risk of heart attack in patients taking Avandia, committee members agreed by a 20-3 margin that the available data do support the conclusion that Avandia increases the risk of cardiac ischemia in type 2 diabetes patients. However, committee members felt that the many problems with the data and the lack of information on the risk associated with other drugs for diabetic patients precluded a justification of withdrawal of Avandia from the market. Several committee members qualified their vote by stating that a black box warning should be included for specific subgroups of patients, including those taking insulin or nitrates, leading to the final recommendation of the inclusion of such a warning.

The majority of the testimony presented throughout the day by the FDA and GSK focused on the findings from the meta-analysis, observational studies, and randomized controlled trials. The meta-analysis performed by the FDA and GSK suffered the same limitations and showed the same results as the meta-analysis performed by Steven Nissen, author of the original article published in the New England Journal of Medicine. All showed that there is a 1.3 to 1.4 hazard ratio for increased cardiac effects of rosiglitazone; however, most of the studies analyzed were short in duration and not designed to look specifically at cardiac events. A number of observational trials that were also analyzed and discussed showed no increased cardiac side effects associated with the drug as compared to other regimens. Finally, testimony from the FDA showed that a number of ongoing large, randomized controlled trials, including RECORD, BARI-2D, and ACCORD, will likely not provide definitive findings on the effects of rosiglitazone on the risk of cardiac events due to design limitations. Because of the conflicting and limited nature of these findings, committee members concurred that the available data are not conclusive enough to justify pulling the drug from the market.

In addition to its attendance at the hearing, the Society submitted written testimony to the committee. The testimony, which may be viewed at the link below, outlined the Society’s recommendation that no precipitous action should be taken by the FDA in regard to rosiglitazone and discussed a number of worrisome characteristics of the Nissen study. The Society supports the decision of the FDA advisory committee to keep rosiglitazone on the market and available to patients while including a warning on the drug's label regarding its possible link to heart disease. To view the Society’s press release on the FDA decision, click on the link below:

Society Press Release on FDA Decision