Avandia (rosiglitazone) is an oral medication for treating type 2 diabetes. The drug’s history is marked by controversy over its therapeutic benefits versus major safety concerns. Approved by the U.S. Food and Drug Administration (FDA) in 1999, its journey from a widely prescribed treatment to a medication of last resort illustrates the complexities of drug safety and regulation.
How Avandia Works to Treat Type 2 Diabetes
Avandia belongs to a class of drugs called thiazolidinediones (TZDs) and functions as an “insulin sensitizer.” It makes the body’s cells, particularly in fat, muscle, and the liver, more responsive to the insulin the pancreas produces. The drug achieves this by activating a specific receptor inside cells known as PPARγ (peroxisome proliferator-activated receptor gamma).
Activation of PPARγ receptors regulates the expression of genes involved in glucose and fat metabolism. By influencing these genes, Avandia helps the body utilize its insulin more efficiently to move sugar from the bloodstream into cells for energy. This process lowers blood glucose concentrations without directly stimulating the pancreas to produce more insulin, a unique action that made it a promising treatment.
The Rise and Fall of Avandia
Following its FDA approval, Avandia quickly became a popular treatment for type 2 diabetes, with annual sales reaching $2.5 billion by 2006. Its novel mechanism of improving the body’s sensitivity to insulin offered a new option for patients. This success was halted by emerging safety concerns that would redefine the drug’s place in medicine.
The turning point occurred in 2007 with a meta-analysis in The New England Journal of Medicine. This analysis, led by cardiologist Steven Nissen, concluded that Avandia was associated with a 43% increased risk of heart attack and a 64% increased risk of death from cardiovascular causes. The findings prompted immediate scrutiny from regulatory bodies worldwide.
In response, the FDA convened advisory committee meetings to assess the drug’s safety. In 2007, the agency mandated a “black box warning”—its most stringent alert—be added to Avandia’s label to highlight the risk of myocardial ischemia. By 2010, the agency implemented a strict Risk Evaluation and Mitigation Strategy (REMS) that severely limited access to the medication and removed it from retail pharmacy shelves.
Re-evaluation and Current Prescription Status
The FDA later required a re-examination of the Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes (RECORD) clinical trial. This re-adjudication, conducted by the Duke Clinical Research Institute, reviewed the original data. It concluded that the trial did not show a statistically significant increased risk of heart attack or death compared to standard diabetes medications.
Based on these new findings, an FDA advisory committee in 2013 voted to modify or remove the strict REMS program. The FDA lifted the prescribing and dispensing restrictions later that year. By 2015, the agency also removed the black box warning related to heart attack risk, stating that its concerns had been “substantially reduced.”
Despite the reversal of these regulatory actions, Avandia has not returned to its former prominence. Lingering concerns among physicians and patients, coupled with the availability of newer diabetes medications with more favorable safety profiles, have kept its prescription rates low. Its complex history has left a lasting impact, making it a rarely used option in contemporary diabetes care.
Significant Side Effects and Health Risks
Beyond the debated cardiovascular issues, Avandia is associated with several other health risks. One of the most prominent is fluid retention, or edema, which can lead to or worsen congestive heart failure. The drug carries a black box warning for this risk and is not recommended for patients with symptomatic heart failure.
Patients taking Avandia may also experience notable weight gain, resulting from a combination of fluid retention and an increase in fat mass. Rapid weight gain can be a sign of dangerous fluid retention.
Another documented risk is an increased incidence of bone fractures, particularly in women. Studies show that long-term use is associated with fractures in the upper arm, hand, and foot. Other potential side effects include liver problems, anemia, and macular edema, a condition involving fluid buildup in the eye.