Use of SGLT2 Inhibitors Versus DPP-4 Inhibitors and Age-Related Macular Degeneration in Patients With Type 2 Diabetes: A Multinational Cohort Study

Abstract

PURPOSE. To compare the impact of sodium–glucose cotransporter 2 (SGLT2) and dipeptidyl peptidase 4 (DPP-4) inhibitors on age-related macular degeneration (AMD) risk among patients with type 2 diabetes mellitus (T2DM). METHODS. This multinational, retrospective cohort study used electronic medical records from healthcare institutions across 21 countries. Adults 50 years or older with T2DM who had a prior prescription of metformin and initiated SGLT2 or DPP-4 inhibitors from 2013 to 2023 were included. The SGLT2 and DPP-4 inhibitor groups were propensity score matched in a 1:1 ratio to balance baseline characteristics and were followed for up to 5 years to observe the occurrence of AMD. Statistical analysis was performed using the Cox proportional hazards model and Kaplan–Meier analysis. RESULTS. Our final analysis included 20,966 T2DM patients prescribed SGLT2 inhibitors and 20,966 prescribed DPP-4 inhibitors. Compared to the DPP-4 inhibitor group, the SGLT2 inhibitor group was associated with significantly lower risks of AMD (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.58–0.85) and dry AMD (HR, 0.61; 95% CI, 0.46–0.80) but not wet AMD (HR, 0.74; 95% CI, 0.48–1.16). SGLT2 inhibitors compared with DPP-4 inhibitors were linked to a reduced risk of AMD in the White population, patients prescribed empagliflozin or dapagliflozin, and individuals with glycated hemoglobin < 8.5%, estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2, hypertension, or dyslipidemia, regardless of body mass index level. CONCLUSIONS. In patients with T2DM, those prescribed SGLT2 inhibitors may experience lower risks of AMD and dry AMD compared to those prescribed DPP-4 inhibitors.