GLP-1 Receptor Agonists and Ischemic Optic Neuropathy in Patients with Type 2 Diabetes and Obesity: A TriNetX Cohort Study

Objective To evaluate coded ischemic optic neuropathy (ION) events among patients with type 2 diabetes mellitus (T2DM) and obesity receiving glucagon-like peptide-1 receptor agonists (GLP-1RAs) compared with patients receiving non-GLP-1RA glucose-lowering therapies. Design Exploratory retrospective cohort study. Subjects Adults aged 18 years or older with T2DM and obesity identified within the TriNetX Global Collaborative Network. Methods Patients were stratified according to exposure to GLP-1RAs or non-GLP-1RA glucose-lowering therapies. Patients with diagnostic codes for giant cell arteritis were excluded during cohort construction. The primary outcome was coded ION, identified using ICD-10-CM H47.01. Propensity score matching (PSM) was performed for demographic characteristics, comorbidities, laboratory variables, insulin and antihypoglycemic medication use, and medications associated with optic neuropathy risk, including amiodarone, sildenafil, and tadalafil. Results After 1:1 PSM, 205,500 patients were included in each cohort. Coded ION events occurred in 134 patients in the GLP-1RA cohort and 143 patients in the comparator cohort, corresponding to absolute risks of 0.065% and 0.070%, respectively. Cumulative risk analysis did not show a statistically significant difference between cohorts, with a risk ratio of 0.937, 95% CI 0.741–1.186. Kaplan-Meier analysis showed survival probabilities of 99.86% and 99.90%, respectively. Cox regression yielded a hazard ratio of 1.271, 95% CI 1.002–1.613. Conclusions In this exploratory EHR-based cohort study, cumulative risk estimates did not detect a statistically significant difference in coded ION events between treatment groups, although time-toevent analysis suggested a small increase in hazard.