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FDA Removes Avandia (rosiglitazone) Restrictions Category: Diabetes by - December 1, 2013 | Views: 23880 | Likes: 2 | Comment: 1  

Avandia, rosiglitazone, FDA restrictions

On November 25, 2013, the FDA announced removal of certain prescribing and dispensing restrictions of rosiglitazone (Avandia, Avandaryl, Avandamet) because of new analysis of its cariovascualr risk profile. Concerns about rosiglitazone causing heart related conditions were fueled by meta-analysis of small clinical trials reported in 2007. 

Following recommendations from expert committees the FDA recommends changing the indication for rosiglitazone containing drugs. The FDA arrived at this decision because of a re-analysis of data obtained from the Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes (RECORD) trial which showed that the risk of heart attack or death in patients being treated with Avandia is similar to standard diabetes drugs. 

The RECORD trial (published 2009) is a multicenter, open-label trial where 4447 patients with poorly controlled (HbA1c 7.9%) type 2 diabetes, despite treatment with metformin or a sulfonylurea,  were randomly assigned to rosiglitazone (n=2220) or a combination of metformin plus a sulfonylurea (n=2227) for 5 to 7 years. After a mean followup of 5.5 years 321 people in the rosiglitazone group compared to 323 people in the combination of metformin plus a sulfonylurea group experienced cardiovascular hospitalization or cardiovascular death. Rosiglitazone was found to be non-inferior to metformin plus a sulfonylurea in the risk of cardiovascular death, heart attack, or stroke. The risk of heart failure causing hospitalization or death was greater in people who received rosiglitazone. Limb fractures, especially in women, were also more frequent in people who received rosiglitazone. A recent re-analysis of the RECORD trial did not change the conclusions of the original analysis.

Critics of the RECORD study point out that the study was open-label and subject to bias. While blinded studies are the gold standard for clinical trials, professionals should also consider that in the absence of blinded studies the next best level of evidence should be considered. Moreover, meta-analysis similar to the publication that suggested an association between rosiglitazone and cardiovascular risk, are also subject to bias and design issues and are less reliable than open-label randomized trials. The rosiglitazone story reminds us once again about the limitations of meta-analysis and why they should only be used for hypothesis. 

The FDA’s current position on rosiglitazone will modify language in rosiglitazone’s prescribing information about cardiovascular safety, modify the Risk Evaluation and Mitigation Strategy (REMS) program, and remove the requirement for one additional post marketing study that would have compared Avandia to Actos (pioglitazone). The indication for rosiglitazone will state that it may be used along with diet and exercise to improve control of blood sugar in patients with type 2 diabetes mellitus. This is similar to the indication for other diabetes medications. The current indication limits use of rosiglitazone to people already taking rosiglitazone or are unable to achieve adequate glycemic control on other diabetes medications and decided not to take pioglitazone (ACTOS) for medical reasons. 

When these changes take effect  

  • Healthcare professionals will no longer need to be enrolled in the REMS program before prescribing or dispensing rosiglitazone. 
  • Patients will no longer need to enroll in the REMS program before receiving rosiglitazone. 
  • Patients can receive rosiglitazone through regular pharmacies and mail order pharmacies. 
  • All patients with type 2 diabetes will be eligible for treatment with rosiglitazone. 


Based on available evidence the FDA is removing rosiglitazone prescribing restrictions imposed because of concerns about risk of cardiovascular effects. More patients will now be eligible to receive rosiglitazone, contributing to options for treating type 2 diabetes. As with all drugs, practitioners should carefully review patient characteristics and risks before prescribing any drugs and should continue to monitor patents during treatment in order to achieve the best outcomes. 


FDA requires removal of certain restrictions on the diabetes drug Avandia

FDA Press Release: FDA requires removal of certain restrictions on the diabetes drug Avandia

Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. The Lancet, Volume 373, Issue 9681, Pages 2125 - 2135, 20 June 2009.

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