Glitazone Use Associated with Diabetic Macular Edema

Glitazone use was associated with an increased risk of diabetic macular edema even after accounting for confounding factors, according to the results of a large, prospective cohort study.

Insulin use and meglitinide use also resulted in statistically significant increases in the risk of diabetic macular edema (ME), the analysis found.
Glitazones (thiazolidinediones) are used to reduce insulin resistance in patients with type 2 diabetes. One of the most commonly used drugs in this class is pioglitazone (Actos). Some studies have found pedal edema in 3%-5% of glitazone users, and others have suggested an association between glitazones and ME.

More than 170,000 persons listed in the Diabetes Case Identification Database were included in a study conducted by Kaiser Permanente Southern California. Glitazone use was based on records in the pharmacy database, and the main outcome measure was the development of ME, according to Dr. Donald S. Fong and Richard Contreras from the Southern California Permanente Medical Group.

For the years 2002-2006, 143,257 patients with diabetes had a drug benefit. Of these, 59,013 patients had at least one eye exam in 2006, and in that year, 996 new cases of ME were identified. In the total population, 17,078 patients were treated with glitazones, 98% of whom were treated with pioglitazone. In a direct comparison, all individuals who were being treated with glitazones showed a higher risk of developing ME in 2006 (odds ratio, 2.6; 95% confidence interval, 2.4-3.0). After excluding patients who did not have a drug benefit or an eye exam and who had an HbA1c level less than 7.0, the investigators found that glitazone use was still associated with an increased risk of ME.

Other drugs showed an increased risk of ME in these patients. Insulin and meglitinide also appeared to increase the risk of diabetic ME.  However, metformin and acarbose use were not associated with ME.

An interactive model that was used to explore the relationship between insulin and glitazone showed that although both drugs separately are associated with an increased risk of ME, the risk is less when individuals take both drugs, according to the researchers. There were no statistically significant differences between different doses of pioglitazone and the risk of ME.

“The current larger study of over 17,000 users of glitazone confirms an association between glitazone use and ME. When treating patients with diabetic ME, ophthalmologists should consider the role of the glitazone class of drugs,” the authors concluded.

American Journal of Ophthalmology, Feb. 2009