Few See Renewed Role for Rosiglitazone in Diabetes

Lisa Nainggolan

Following the US Food and Drug Administration (FDA) decision yesterday to lift the restrictions on the type 2 diabetes drug rosiglitazone (Avandia, GlaxoSmithKline) and any rosiglitazone-containing products or generics, the big question now is whether the product will ever be "resurrected."

Rosiglitazone is currently taken by only a few thousand patients in the United States as a result of the very strict prescribing restrictions that were put in place in 2010 due to concerns about cardiovascular safety of the agent.

Following the US FDA’s announcement that it will lift these requirements, US patients will soon be able to receive rosiglitazone through regular pharmacies, and the agency is also releasing GlaxoSmithKline from the postmarket requirement to conduct a clinical trial, TIDE, comparing rosiglitazone and pioglitazone, the only other approved drug in the thiazolidinedione class of diabetes agents.

But none of the experts that Medscape Medical News spoke with today believe this will have much material impact on the use of rosiglitazone.

The general consensus appears to be that too much water has passed under the bridge: patients have been hearing about cardiovascular safety concerns relating to rosiglitazone for years and are unlikely to be reassured by yesterday’s FDA decision; likewise doctors. Also, since the thiazolidinediones were first introduced in 2007, a host of new agents for type 2 diabetes have been introduced. 

And those who do require a thiazolidinedione can use pioglitazone instead, which is available generically.

In Europe, where rosiglitazone has been suspended since 2010, Medscape Medical News understands that GlaxoSmithKline has no intention of trying to reintroduce the drug.

The European Medicines Agency (EMA) said today: "So far, the marketing authorization holder [GlaxoSmithKline] has not requested the EMA to undertake a new assessment of the evidence with a view to identifying a patient population in whom the benefits of these [rosiglitazone-containing] medicines outweigh their risks, which is required in order for their suspension to be lifted.

"Should it be asked to do so, the EMA will assess the total evidence carefully and consider any appropriate action."

Rosiglitazone is still marketed by GlaxoSmithKline in a number of countries worldwide, however. As well as the United States, these are: Algeria, Argentina, Australia, Canada, Chile, China, Costa Rica, Honduras, Hong Kong, Jamaica, Macao, Malaysia, Mexico, Myanmar, Republic of Korea, Russian Federation, Singapore, and Taiwan.

FDA "Saving Face" in Lifting Restrictions on Rosiglitazone 

Although his views will come as absolutely no surprise, long-time critic and one of the authors of the 2007 meta-analysis that first suggested an increased risk for heart attack with rosiglitazone, cardiologist Steve Nissen, MD, from the Cleveland Clinic, Ohio, told Medscape Medical News that yesterday’s decision by the FDA "does not serve the public interest.

"It is based entirely upon a reanalysis of a poorly designed, open-label European clinical trial [RECORD] that would not meet any reasonable regulatory standard. All other analyses show an elevated cardiovascular risk for rosiglitazone.

"Fortunately, physicians will not use this drug again," Dr. Nissen said, reminding people that "the company [GlaxoSmithKline] pleaded guilty to civil and criminal charges, in part related to rosiglitazone, and paid a $3 billion fine, one of the largest in US history."

David Juurlink, MD, PhD, of Sunnybrook Health Sciences Centre, in Toronto, Ontario, agreed: "Yesterday’s announcement from the FDA was simply about saving face. Perhaps they rationalize lifting the restrictions because they realize that Avandia is dead in the water and that no sensible physician would want to prescribe it anyway."

He is equally critical of his home country. "Health Canada didn’t have the fortitude to pull [rosiglitazone] either. They passed the buck to MDs and pharmacists, instructing them to "get consent" from patients who were prescribed the drug. This did effectively kill the drug, but it was a bit of a weasel strategy for a national regulator."

Although Dr. Juurlink concedes that the reanalysis of RECORD allays some concerns, the key question, he believes, relates to the general cardiovascular safety of rosiglitazone. "The reanalysis of RECORD does not bear on that question, but common sense sure does.


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