Last week, an advisory panel convened by the U.S. Food and Drug Administration (FDA) voted to relax safety restrictions on the diabetes drug rosiglitazone (Avandia) that were put in place in response to previous evidence that rosiglitazone may increase the risk of heart attacks and cardiovascular deaths. American Family Physician first highlighted these safety concerns in its March 15, 2008 Tips From Other Journals, which Dr. Kenneth Moon concluded:
There is substantial circumstantial evidence that rosiglitazone is associated with higher risks of heart failure and myocardial infarction. Despite the awkwardness of persuading a patient to use a drug that may provide similar benefits but pose greater risks than other proven agents, the legitimate concerns raised by these studies make this a serious issue. Until there is conclusive evidence about the safety of rosiglitazone, many physicians and their patients may be more comfortable using alternative treatments.
Subsequent AFP articles on management of blood glucose in type 2 diabetes and rosiglitazone vs. pioglitazone reinforced cautionary messages about rosiglitazone. However, the results of a large randomized trial published in 2009 found similar risks for cardiovascular hospitalizations and death in patients using rosiglitazone compared to patients taking other oral diabetes drugs. This trial, which was sponsored by rosiglitazone's manufacturer GlaxoSmithKline, was criticized for methodological problems, but an independent re-analysis of the trial's data persuaded the FDA advisory panel that the drug's safety risks had been exaggerated in previous studies.
If the FDA acts on the advisory panel's recommendations and makes rosiglitazone more widely available, should family physicians prescribe it? It is worth noting that the panel considered only the drug's safety, not its effectiveness. A previous AFP Journal Club reminded readers that the disease-oriented outcome of improved glycemic control does not necessarily lead to patients living longer or better. Rosiglitazone causes more weight gain and congestive heart failure than metformin, and is more expensive than metformin and sulfonylureas. For those reasons, it should be a second- or third-line drug choice for patients with type 2 diabetes.