Although thiazolidinedione products may be effective for controlling blood sugar levels, these drugs have been linked to potentially serious heart complications. Rosiglitazone and pioglitazone are the two drugs in the thiazolidinedione class, and both have received black box warnings from the FDA. These warnings state that these products can increase the risk for heart failure and may cause or exacerbate heart failure symptoms.
What Are Thiazolidinediones?Thiazolidinediones are a group of prescription medications approved for the treatment of type 2 diabetes. These medications work by improving the body's natural response to insulin. Troglitazone (Rezulin®) was the first drug in this class approved by the U.S. Food and Drug Administration (FDA) in 1997, but was withdrawn from the market in 2000 due to the drug's potential to cause liver damage.
Rosiglitazone (Avandia®) and pioglitazone (Actos®) are the two drugs in the thiazolidinedione class that are currently available in the United States. These two products are also available in combination prescription products, including:
- Rosiglitazone and glimepiride (Avandaryl®)
- Rosiglitazone and metformin (Avandamet®)
- Pioglitazone and glimepiride (Duetact®)
- Pioglitazone and metformin (Actoplus Met®)
- Pioglitazone and metformin XR (Actoplus Met® XR).
Rosiglitazone (Avandia) was initially approved in May 1999. Shortly thereafter, the combination products rosiglitazone and metformin (Avandamet) and rosiglitazone and glimepiride (Avandaryl) were available in the United States in 2002 and 2005, respectively.
In the early 2000s, studies began showing a correlation between heart failure and thiazolidinedione use. By 2007, enough data was collected to support this correlation, and the FDA issued a "black box warning" on all available thiazolidinedione products. The black box warning stated that this drug class is not recommended for use in people with heart failure and that these drugs may cause or exacerbate heart failure symptoms.
In addition, in 2007, the FDA required the label on rosiglitazone products to contain a statement that said these products have been linked to an increase in heart attacks in some studies; however, the results of these studies were not yet conclusive.
In 2010, more conclusive data showed that rosiglitazone products did increase the risk for heart attacks in people with type 2 diabetes. On September 23, 2010, the FDA announced that it would significantly restrict the use of rosiglitazone products to people who could not adequately control blood sugar levels with other medications. This announcement resulted in a 50 percent decrease in rosiglitazone prescriptions from January 2010 to October 2010.
As of November 18, 2011, rosiglitazone products (Avandia, Avandryl, Avandamet) are unavailable at local pharmacies. Instead, the FDA is mandating that people must be enrolled in a program called the Avandia-Rosiglitazone Medicines Access program to receive these products through one special mail-order pharmacy only. This new program will restrict the use of rosiglitazone products to the following types of people:
- Those who are already being successfully treated on the medication
- Those whose blood sugar levels cannot be controlled using any other medication
- Those who do not wish to take pioglitazone-containing medicines after consulting with their healthcare provider.