Empagliflozin and the Risk of Retinopathy in Patients With Type 2 Diabetes

ImportanceEmpagliflozin might lower the risk of diabetic retinopathy (DR) by preventing retinal pericyte loss. However, the role of empagliflozin with respect to DR in patients with type 2 diabetes (T2D) remains unclear.ObjectiveTo compare the risk of incident nonproliferative DR (NPDR) and DR progression in patients with T2D initiating empagliflozin vs a dipeptidyl peptidase 4 inhibitor (DPP4i).Design, Setting, and ParticipantsA new-user active-comparator cohort study was conducted using US nationwide insurance claims data from 2 commercial insurers and Medicare from August 2014 to September 2019. Adults with T2D initiating study drugs without prior diagnosis or treatment for proliferative DR or other advanced retinal diseases were included. To assess incident NPDR, patients with a history of NPDR were additionally excluded, while for the DR progression outcome, patients were required to have a history of NPDR. Data were analyzed from August 2022 to May 2024.ExposuresInitiation of empagliflozin or a DPP4i.Main Outcomes and MeasuresIncident NPDR was defined using diagnostic codes for mild, moderate, or severe NPDR. The DR progression outcome was defined as a composite of incident proliferative DR, vitreous hemorrhage, initiation of intravitreal anti–vascular endothelial growth factor injection, or panretinal photocoagulation. Incidence rates, hazard ratios (HRs), and rate differences (RDs) with 95% CIs were estimated.ResultsA total of 34 239 pairs of propensity-score matched adults were identified in the incident NPDR cohort and 7831 pairs in the DR progression cohort. In the incident NPDR cohort, 35 867 patients (52.4%) were male, and the mean (SD) age was 65.6 (10.3) years. In the DR progression cohort, 8229 patients (52.5%) were male, and the mean (SD) age was 67.0 (10.0) years. Over a mean (SD) follow-up period of 8 (7.5) months receiving treatment, the risk of incident NPDR was not different across groups (HR, 1.04; 95% CI, 0.94 to 1.15; RD, 1.30; 95% CI, −1.83 to 4.44), while the risk of DR progression was lower among individuals who initiated empagliflozin compared with those who began DPP4i therapy (HR, 0.78; 95% CI, 0.63 to 0.96; RD, −9.44; 95% CI, −16.90 to −1.98). Results were consistent across multiple subgroups and sensitivity analyses.Conclusions and RelevanceCompared with initiation of a DPP4i, empagliflozin initiation was not associated with incident NPDR, although it may be associated with a lower risk of DR progression. Although residual confounding cannot be entirely ruled out due to the observational nature of our study, these findings may be helpful when weighing the risks and benefits of various glucose-lowering agents in adults with T2D.