Objective: To investigate the association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and nonarteritic ischemic optic neuropathy (NAION).
Research design and methods: The PubMed, Embase, and Cochrane Library databases were searched during August 2025. Odds ratios (ORs) and absolute risk for NAION values were pooled using random-effects Peto and inverse-variance models. Any ocular event was a secondary outcome.
Results: Fifteen longitudinal studies (n = 8 trials; n > 1.5 million patients) were included. GLP-1 RA use was associated with higher NAION risk (OR 1.70; 95% CI 1.23-2.36), consistent across randomized (2.36; 0.85-6.53) and nonrandomized studies (1.64; 1.15-2.35) (P = 0.51, for heterogeneity). Absolute NAION risk in the GLP-1 RA group was 0.09%, corresponding to a 0.037% risk difference (number needed to harm ∼ 2,700). There was no association with overall ocular events (OR 0.95; 95% CI 0.86-1.05).
Conclusions: GLP-1 RA use was associated with a modest increase in NAION risk but not overall ocular adverse events. Findings underscore the need for long-term postmarketing safety studies and should be interpreted against their well-established mortality and cardio-kidney-metabolic benefits.
© 2025 by the American Diabetes Association.