GLP1-RA Use and Risk of Non-arteritic Anterior Ischemic Optic Neuropathy in Patients with Type 2 Diabetes.

IMPORTANCE: Concerns have been raised regarding the increased risk of non-arteritic ischemic optic neuropathy (NAION) associated with the use of glucagon-like peptide 1 receptor agonist (GLP-1 RA). However, findings remain inconsistent due to differences in indications for drug use, comparator groups, follow-up periods, and study populations. OBJECTIVE: This study aims to examine the association between GLP-1 RA use and the risk of NAION among U.S. patients with type 2 diabetes mellitus (T2DM) enrolled in private health plans. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted based on health administrative claims data from 2012 to 2024. Target trial emulation was applied, using a new user design and active comparators, to compare the risk of NAION between patients initiating GLP-1 RAs and those initiating sodium-glucose cotransporter-2 inhibitors (SGLT-2i) or dipeptidyl peptidase-4 inhibitors (DPP-4i). Propensity score methods were utilized to balance baseline demographic and clinical characteristics between the comparison groups. Cox proportional hazard models were applied to estimate adjusted hazard ratios (HR) of NAION incidence associated with GLP-1 RAs, relative to SGLT-2i or DPP-4i. EXPOSURES: Participants initiating GLP-1 RAs compared with those initiating SGLT-2i or DPP-4i for the treatment of T2DM. MAIN OUTCOMES AND MEASURES: Incidence of NAION in the comparison groups and the adjusted hazard ratios between groups. RESULTS: A total of 19,505 adult patients diagnosed with T2DM were included, with 9,213 (47.2%) using GLP-1 RAs, 10,292 (52.8%) exposed to SGLT-2i or DPP-4i, and 29 incidences of NAION. Compared with SGLT-2i or DPP-4i, overall GLP-1 RA use was not significantly associated with a higher risk of NAION (HR: 1.87; 95%CI: 0.85-4.12). However, risk of NAION among liraglutide users was higher than for SGLT-2i or DPP-4i users within 12 or 18 months of follow-up. Additionally, the elevated risk of NAION associated with GLP-1 RAs relative to SGLT-2i or DPP-4i was observed in males and older adults. CONCLUSIONS AND RELEVANCE: Our findings indicate that GLP-1 RA use, particularly liraglutide, may be associated with an increased risk of NAION among patients with T2DM. Further research is warranted to confirm these findings and clarify the biological mechanisms linking GLP-1 RA use to NAION.