Lu_2025_Ophthalmol.Sci_5_100827

PURPOSE: To investigate the association between dipeptidyl peptidase-4 inhibitors (DPP4is) and the risk of primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG) in patients with type 2 diabetes mellitus (T2DM). DESIGN: Retrospective cohort study. SUBJECTS: A total of 582 710 patients with T2DM treated with either DPP4i (exposure group) or non-DPP4i medications (control group) were analyzed between 2008 and 2021. METHODS: Patients were 1-to-1 matched by propensity scores on demographic and clinical characteristics. Cox proportional hazards models were applied to estimate hazard ratios for POAG and NTG, adjusting for age, sex, comorbidities, and concurrent antidiabetic medications. MAIN OUTCOME MEASURES: Incidences of POAG and NTG. RESULTS: Dipeptidyl peptidase-4 inhibitor users demonstrated a significantly lower risk of POAG (adjusted hazard ratio [aHR], 0.53; 95% confidence interval [CI], 0.50-0.56) and NTG (aHR, 0.55; 95% CI, 0.50-0.62) compared to non-DPP4i users on first-generation diabetes medication. Subgroup analysis revealed a consistent risk reduction across all age groups (18-39: aHR, 0.56; 95% CI, 0.51-0.62; 40-64: aHR, 0.52; 95% CI, 0.47-0.57; <=65 years: aHR, 0.51; 95% CI, 0.47-0.56) and among patients with or without diabetic-related complications, including diabetic retinopathy, diabetic kidney disease, and diabetic neuropathy (DN) (aHR: without vs. with diabetic retinopathy [0.54 vs. 0.43], without vs. with diabetic kidney disease [0.53 vs. 0.49], without vs. with DN [0.54 vs.0.43]), with all comparisons showing statistical significance (P < 0.001). Cumulative incidence analyses revealed a sustained lower risk for DPP4i users throughout the study period (log-rank P < 0.001). CONCLUSIONS: Exposure to DPP4i was associated with a reduced risk of developing POAG and NTG compared with users of first-generation diabetes medication. Further research is needed to explore the underlying mechanisms and their implications for glaucoma prevention and management. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.