Avandia, Actos May Raise Risk of Macular Edema

July 2nd, 2012
written by Michael O’Leary

In a large observational study there appears to be a link between a commonly used drug for type 2 diabetes and an increased risk of macular edema, or swelling of the base of the retina, which is responsible for central vision.


(Published site)


The study was published online ahead of print by the journal Archives of Internal Medicine, and while it is far from conclusive, it raises awareness among doctors caring for people with type 2 diabetes to watch for signs of blurred vision in those taking the drugs.

As reported by MedPage Today, the study involved an analysis of data collected by The Health Improvement Network (THIN), a large ongoing study of 103,368 people in England with type 2 diabetes and without macular edema at the start of the study.

They found that the 3,227 patients among the study group who used pioglitazone (ACTOS) or rosiglitazone (AVANDIA) were 5.7-fold more likely to develop diabetic macular edema than those who didn’t take the drugs. The medications belong to a family of drugs called thiazolidinediones, or TZDs.

After adjusting for age, blood pressure, cholesterol levels, HbA1c, use of aspirins, and other characteristics of the population to eliminate any chance that there was something about the way the patients were selected for the study that produced the result, they still found that those taking ACTOS or AVANDIA had 2.3 times the risk of macular edema.

While that sounds alarming, the number of people with type 2 diabetes that develop macular edema is small. About 1.3 percent of people with type 2 diabetes who take thiazolidinedione (TZD) develop the condition after one year of taking the drug.

While there is a biological connection between the drugs this type of observational study cannot determine if taking the drugs actually causes the condition. This type of study is only able to identify a statistical link between the two. Nevertheless these types of studies are useful in identifying things, in this case a type of drug that ought be studied to see if they do cause an adverse effect that had not been found in the studies that led to FDA approval.

The biological connection is that the drugs activate a protein that decreases the amount of glucose released by the liver, but that protein is also found in the blood vessels of the retina and may contribute to fluid retention there.

The authors of this study did caution that other studies of this issue have produced conflicting results, and this study itself has limitations. They did not take into consideration how long participants had been taking the drugs, or had been diagnosed with type 2 diabetes, primarily because that information had not been collected in the database.

Despite the limitations, however, the report has prompted a caution for doctors whose patients are taking ACTOS or AVANDIA. Rosiglitazone (AVANDIA) has been restricted in the U.S. and was removed from the market in Europe due to an increased risk of cardiovascular effects.