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

Jan 12, 2026Cureus

GLP-1 Therapy and Sudden Vision Loss from Non-Inflammatory Optic Nerve Damage

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Abstract

Over a five-year period, the risk of nonarteritic anterior ischemic optic neuropathy (NAION) is increased by 0.022% in type 2 diabetes patients treated with GLP-1 receptor agonists.

Patients treated with GLP-1 receptor agonists showed a risk ratio of 1.339 for developing NAION compared to those not treated.
A total of 776,666 patients were analyzed after matching for 20 covariates.
The confidence interval for the risk difference was between 0.01% and 0.034%, indicating a statistically significant finding.
E-value sensitivity analysis suggested a moderately robust association between GLP-1 treatment and NAION risk.
The underlying mechanism linking GLP-1 therapy to NAION is still not understood.

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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.