Impact of GLP-1 Agonists and SGLT-2 Inhibitors on Diabetic Retinopathy Progression: An Aggregated Electronic Health Record Data Study.

Purpose: To examine the effects of glucagon-like peptide-1 receptor (GLP-1) agonists compared to SGLT-2 inhibitors on diabetic retinopathy.

Design: Retrospective clinical cohort study using TriNetX, a federated electronic health records network comprising multiple healthcare organizations.

Methods: Patients with an International Classification of Diseases, Tenth Revision (ICD-10) code of nonproliferative diabetic retinopathy (PDR) and monotherapy treatment, excluding insulin, with GLP-1 agonists or SGLT-2 inhibitors. Patients with a history of PDR prior to initiation of treatment were excluded. The rate of progression to PDR and rate of development of diabetic macular edema (DME) were compared between patients on GLP-1 agonists compared to those on SGLT-2 inhibitors. The groups were propensity score matched for age, gender, ethnicity, race, type of diabetes, and severity of PDR. Main outcomes included rate and relative risk (RR) of progression to PDR and risk of DME in the GLP-1 agonist group versus the SGLT-2 inhibitor group.

Results: A total of 6481 patients were identified in the GLP-1 cohort and the SGLT-2 inhibitor cohort after propensity score matching. At 1 and 3 years after initiation of therapy, a higher rate of progression of PDR was noted (RR: 1.26, CI 1.04-1.51, P = .017 at 1 year, RR: 1.284, CI 1.1-1.499, P = .002 at 3 years) in the GLP-1 agonist cohort compared to the SGLT-2 inhibitor cohort. There was a higher rate of DME noted at 3 months (RR: 1.192, CI 1.059-1.276, P = .002), 6 months (RR: 1.22, CI 1.13-1.32, P < .001), 1 year (RR: 1.24, CI 1.15-1.33, P < .001), and at 3 years (RR: 1.29, CI 1.21-1.38, P < .001) in the GLP-1 agonist cohort compared to the SGLT-2 inhibitor cohort.

Conclusions: A higher rate of progression of PDR and risk of new-onset DME was observed in patients on monotherapy with GLP-1 agonists compared to those on SGLT-2 inhibitors. It is important for clinicians to be aware of these potential effects and to consider the current retinopathy status when initiating treatment with newer hypoglycemic agents to ensure these patients are appropriately monitored for developing potential vision-threatening complications.