Dahr research explores role of medications in DME risk
A recent study led by Sam Dahr, MD, professor and Mary Farish Johnston Distinguished Chair in Ophthalmology, and Texas A&M medical student Jawad Muayad, examined how commonly prescribed systemic medications may influence the risk of developing diabetic macular edema (DME).
The research, published in Ophthalmology Retina Journal, leveraged a large U.S. patient database to investigate medication effects beyond the traditional focus on blood sugar and blood pressure — two factors long considered central to diabetic retinopathy care.
For the past 15 years, retina specialists have primarily concentrated on delivering treatments directly into the eye to manage DME, the leading cause of vision loss in diabetic retinopathy. However, clinical experience suggested to Dahr that other systemic factors might significantly affect disease progression, which led the team to examine whether certain non-ophthalmic medications might influence DME risk, particularly in patients whose disease course did not align with their blood sugar or blood pressure control.
Using TriNetX, a national database accessible through Texas A&M, the researchers conducted a retrospective cohort study covering a 20-year period spanning from 2004 to 2024. The analysis focused on adults with type 2 diabetes and examined four medication classes: calcium channel blockers (commonly used for hypertension), fenofibrate (a lipid-lowering drug), thiazolidinediones (TZDs, an older class of oral diabetes drugs), and GLP-1 receptor agonists (such as semaglutide, known for both diabetes and weight loss indications). To ensure comparability, the team applied propensity score matching, a statistical method designed to reduce bias in retrospective data analysis.
The findings revealed distinct patterns. Calcium channel blocker use was associated with an increased risk of developing DME compared with patients who were not taking the drug. In contrast, GLP-1 receptor agonists were linked to a 23 percent lower risk of DME, and fenofibrate was linked to a 17 percent lower risk — confirming trends seen in prior studies for fenofibrate. TZD use showed no statistically significant effect.
“Our analysis showed that there may be a protective effect of GLP-1 receptor agonists with regards to diabetic macular edema,” Dahr said. “This paper is actually the first paper in the literature to suggest a potentially protective effect.”
The GLP-1 finding is particularly significant given the class’s complex history with diabetic retinopathy. Early clinical trials for semaglutide raised concerns about an “early worsening phenomenon,” a short-term worsening of retinopathy seen with rapid blood sugar improvement. Although the FDA label still carries a cautionary note, the current study suggests that, over time, GLP-1 receptor agonists may confer a net benefit for retinal health.
Future research will aim to validate these findings in prospective, randomized clinical trials. The team hopes to engage government agencies and pharmaceutical companies in funding such studies, noting that the results should encourage retina specialists to look beyond intravitreal injections and consider broader systemic influences on retinal disease.
The paper was accompanied by an editorial written by Dr. Paolo S. Silva of the Joslin Diabetes Center and Harvard Medical School. As Silva noted, “Although glycemic and blood pressure control remain cornerstones of diabetic retinopathy and diabetic macular edema prevention, these findings highlight the underrecognized complexities surrounding systemic medication use.”
Contributing authors to the story include Muayad; Asad Loya, MD; Zain S. Hussain; Debora H. Lee, MD; Muhammad Z. Chauhan, MD, MS; Andrew G. Lee, MD; Asadolah Movahedan, MD; and Dahr.