Sight Unseen: Glucagon-Like Peptide-1 (GLP-1) Agonism Therapy and Nonarteritic Anterior Ischemic Optic Neuropathy

Introduction Nonarteritic anterior ischemic optic neuropathy (NAION) is one of the most common causes of blindness among adults. Numerous risk factors have been noted (such as systemic diseases and medications); however, the underlying pathophysiology has yet to be elucidated. In recent years, however, glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as a cause of NAION, albeit evidence is mixed. As a result, the primary objective of this study is to further analyze the risk of NAION over a five-year period in type 2 diabetes mellitus patients treated with GLP-1 receptor agonists. Methods We utilized TriNetX Global Collaborative Network to perform a retrospective cohort analysis, using de-identified patient data. Patients were divided into two cohorts (cohort A: type 2 diabetes mellitus with GLP-1 treatment; cohort B: type 2 diabetes mellitus without exposure to GLP-1). One-to-one propensity-score matching was employed for n = 20 covariates. We employed a measure of association, calculating risk difference, risk ratio, and 95% confidence interval. Furthermore, those with the outcome of interest (NAION) prior to the index event were excluded from analysis. Results After propensity-score matching, we arrived at n = 388,333 per cohort (n = 776,666 total). Over a five-year period, cohort A demonstrated a statistically significant increased risk of NAION (risk difference 0.022%, 95% CI 0.01%-0.034%; risk ratio 1.339, 95% CI 1.137-1.577, p = 0.005). Additionally, E-value sensitivity analysis confirmed a moderately robust association. Conclusion Whilst of statistical significance, the implicated clinical significance is less concrete, due to a well-established strong benefit-to-risk ratio with the therapeutic class. The exact mechanism of NAION in relation to GLP-1 therapy remains unknown. Further prospective studies are required to evaluate such findings and adjust existing guidelines as appropriate.