OR08-07 Real-World Evidence on GLP-1 Analogues: Insights into NAION Risk in Type 2 Diabetes Mellitus Patients

Abstract Disclosure: M.J. Barnett: None. J.R. Lam: None. C. Casipit: None. A. Rivadeneira: None. Introduction: Glucagon-like peptide-1 (GLP-1) analogues have shown potential benefits in managing type 2 diabetes mellitus (T2DM). This study evaluates the impact of GLP-1 use on ischemic optic neuropathy (NAION) and all-cause mortality compared to non-GLP-1 users within a global health research network. Objectives: The primary objectives were to compare NAION risk and all-cause mortality between cohorts using GLP-1 (Cohort A) and not using GLP-1 (Cohort B), considering demographic characteristics, propensity score matching, and statistical measures of association. Methods: This retrospective cohort study included T2DM patients from the TriNetX Global Collaborative Network. Both cohorts had 381,577 patients after matching. Propensity score matching balanced demographic, clinical characteristics, comorbidities, medications, and HbA1C levels. Outcomes included NAION and all-cause mortality assessed over a 5-year follow-up. Relative risks (RR) and 95% confidence intervals (CI) quantified the outcomes, with the exclusion of patients with prior outcomes. Results: The average age in the population was 62 years old, 50% male to females, an average BMI of 34kg/m2, and an average HbA1C of 8%. NAION risk was slightly higher in the GLP Cohort (293 patients or 0.08%) vs the No GLP Cohort (234 patients or 0.06%) (RR = 1.25, 95% CI: 1.05-1.48, p = 0.011). All-cause mortality was significantly lower in the GLP Cohort (4.0% vs. 9.5%; RR = 0.42, 95% CI: 0.42-0.43, p < 0.001). The hazard ratio for mortality favored GLP-1 use (HR = 0.39, 95% CI: 0.38-0.39, p < 0.001), with survival probabilities of 91.88% (Cohort A) vs. 81.75% (Cohort B). Conclusion: While a slight increase in NAION risk is associated with GLP-1 analogs, the incidence of NAION in both cohorts is very small. The substantial mortality benefit highlights their role in improved glucose control and weight loss. With better long-term glycemic control, the risk of micro and macrovascular complications may also be lower. These findings support using GLP-1 analogs as a safe and effective option in T2DM management, with benefits outweighing the risks for most patients. Presentation: Saturday, July 12, 2025