FDA Lifts Restrictions on Avandia

No increased risk of heart attacks seen in patients with diabetes prescribed rosiglitazone (Avandia)

After reviewing recent data, the US Food and Drug Administration (FDA) has determined that rosiglitazone-containing drugs, such as Avandia, Avandamet, Avandaryl, and generics, do not increase the risk of heart attack compared to the standard type 2 diabetes medicines metformin and sulfonylurea. As a result, FDA is lifting the prescribing and dispensing restrictions for rosiglitazone medicines that were put in place in 2010.

According to a press release from the FDA, the decision to lift the ban was based on review of data from a large, long-term clinical trial and is supported by a comprehensive, outside, expert re-evaluation of the data conducted by the Duke Clinical Research Institute (DCRI).

The FDA anticipates that the new indication will state that the drug may be used along with diet and exercise to improve control of blood sugar in patients with type 2 diabetes mellitus and will not be restricted to patients who are unable to achieve adequate glycemic control on other diabetes medications, and, in consultation with their healthcare provider, have decided not to take pioglitazone for medical reasons.


Previous data from a large, combined analysis of mostly short-term, randomized clinical trials of rosiglitazone had suggested an elevated risk of heart attack, so FDA required a Risk Evaluation and Mitigation Strategy (REMS), called the Rosiglitazone REMS program. The Rosiglitazone REMS program restricted the use of rosiglitazone medicines to help ensure that their benefits outweighed the risks.

Although some scientific uncertainty about the cardiovascular safety of rosiglitazone medicines still remains, the decision to lift the ban was made based on results from the Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes (RECORD) tria. The trial did not show an elevated risk of heart attack or death in patients being treated with rosiglitazone compared to standard-of-care diabetes drugs, as was found in a meta-analysis of clinical trials reported in 2007.

In light of the new re-evaluation of the RECORD trial, the FDA noted that its "concern is substantially reduced." 

“Our actions today reflect the most current scientific knowledge about the risks and benefits of this drug,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research. “Given these new results, our level of concern is considerably reduced; thus, we are requiring the removal of certain prescribing restrictions.”

Expert Agrees with FDA

“I am glad to see the FDA looking critically at data and being less prone to media manipulation and hyperbole,” commented Robert E. Ratner, MD, Chief Scientific and Medical Officer of the American Diabetes Association (ADA). “I think the FDA made the best decision based on the data that they have. It was unfortunate that we have gone through a period of 5 years trying to reconcile all of this data,” he said.

“I think it is unlikely that you are going to see a resurgence in growth of rosiglitazone in part because of the bad publicity that has taken place over the past 5 years and in part because of the availability of an alternative—pioglitazone,” Dr. Ratner said. “Since [these agents] are both now generic, one has to ask the question of why would someone choose rosiglitazone over pioglitazone?,” he said.

“It is very clear that this class of agents is not recommended for patients with underlying heart failure,” Dr. Ratner said. “On the other hand there are other circumstances in which this class of agent would be really attractive. And so I would encourage patients and health care providers to look at individual pros and cons of this class of agent,” he added.

FDA Recommendation

The FDA recommends that patients with type 2 diabetes should continue to work closely with their health care professionals to determine treatment options that are most appropriate. Health care professionals, pharmacies, and patients will no longer be required to enroll in the rosiglitazone REMS program to be able to prescribe, dispense, or receive rosiglitazone medicines. As part of the REMS, sponsors will ensure that health care professionals who are likely to prescribe rosiglitazone medicines are provided training based on the current state of knowledge concerning the cardiovascular risk of rosiglitazone medicines.

FDA Actions

The FDA’s actions include requiring modifications to labeling about cardiovascular safety, requiring changes to the REMS program, and releasing a postmarket study requirement. Once the changes to the REMS are finalized, health care professionals, pharmacists, and patients will no longer be required to enroll in the rosiglitazone REMS program to prescribe, dispense, or receive rosiglitazone medicines. Patients also will be able to receive rosiglitazone through regular retail pharmacies and mail order pharmacies.

Manufacturers will also send Dear Healthcare Provider and Dear Professional Society letters to educate prescribers about the new information.

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