The effect of GLP-1 receptor agonists on diabetic retinopathy at a tertiary care center

Objective The potential association between diabetic retinopathy (DR) worsening and GLP-1 receptor agonists (GLP-1RA) has affected therapeutic management of diabetic patients but remains controversial. This study compared rates of diabetic retinopathy development or progression in patients on GLP-1RA to those on SGLT-2 inhibitors (SGLT-2I). Design Retrospective cohort study. Subjects 981 patients with diabetes mellitus taking GLP-1RA or SGLT-2I, the latter serving as controls, between 2012 and 2023. Methods Patients were one-to-one greedy matched by propensity scores on race/ethnicity, age, smoking status, baseline BMI and HbA1C %, type of diabetes mellitus, baseline DR status and history of DR procedures, duration of drug use, whether they had taken both drug types, and change in HbA1C % after one year on the drug. Main Outcome Measures The primary outcome was clinical DR development or progression (termed “worsening”) detected by ICD-10 codes, confirmed by manual review, on GLP-1RA compared to SGLT-2I after propensity score matching. Secondary outcomes included DR worsening indicated by need for procedures due to complications, and time-to-first DR worsening event. Results The study included 692 GLP-1RA users and 289 SGLT-2I users. The mean follow-up periods for GLP-1RA vs. SGLT-2I use were 1.54 (SD 1.82) years and 1.38 (SD 1.56) years, respectively. The rates of clinical worsening were 2.3% and 2.8%, respectively. After propensity score matching, an association was not identified between GLP1-RA and DR worsening neither clinically by ICD-10 codes (OR=0.33, 95% CI 0.11-1.03) nor by indication for procedures (OR=0.50, 95% CI 0.13-2.00). Time-to-first DR worsening did not differ between the groups in Kaplan-Meier analysis.The most common type of clinical worsening event for both drug types was vitreous hemorrhage (43.7% and 50% of worsening events in GLP-1RA and SGLT-2I users, respectively). The most common DR procedure indicated was anti-VEGF injections (34% and 35% of GLP-1RA and SGLT-2I events, respectively). Conclusions DR worsening, either clinically or by procedures, was not associated with GLP-1RA compared to SGLT-2I, both before and after propensity score matching on all analyses, including time-to-first worsening event.