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 GLP-1 agonists compared to SGLT-2 inhibitors on diabetic retinopathy. Design Retrospective clinical cohort study using TriNetX (Cambridge, MA, USA), a federated electronic health records network comprising multiple healthcare organizations. Methods Patients with an International Classification of Diseases, Tenth Revision (ICD-10) code of non-proliferative diabetic retinopathy and monotherapy treatment, excluding insulin, with GLP-1 agonists or SGLT-2 inhibitors. Patients with history of proliferative diabetic retinopathy prior to initiation of treatment were excluded. Rate of progression to proliferative diabetic retinopathy and rate of development of diabetic macular edema 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 non-proliferative diabetic retinopathy. Main outcomes included rate and relative risk of progression to proliferative diabetic retinopathy and risk of diabetic macular edema 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 year and 3 years after initiation of therapy, a higher rate of progression of proliferative diabetic retinopathy was noted (RR: 1.26, CI 1.04-1.51, p=0.017 at 1 year, RR: 1.284, CI 1.1-1.499, p=0.002 at 3 years) in the GLP-1 agonist cohort compared to the SGLT-2 inhibitor cohort. There was a higher rate of diabetic macular edema noted at 3 months (RR: 1.192, CI 1.059-1.276, p=0.002), 6 months (RR: 1.22, CI 1.13-1.32, p<0.001), 1 year (RR: 1.24, CI 1.15-1.33, p<0.001), and at 3 years (RR: 1.29, CI 1.21-1.38, p<0.001) in the GLP-1 agonist cohort compared to the SGLT-2 inhibitor cohort. Conclusions A higher rate of progression of proliferative diabetic retinopathy and risk of new-onset diabetic macular edema 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.