Semaglutide and Nonarteritic Anterior Ischemic Optic Neuropathy: Notoriety Bias or True Ocular Toxicity?
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Objective
To determine whether the semaglutide–NAION association reflects true toxicity or reporting bias.
Research design and methods
We performed temporal disproportionality analysis of FDA Adverse Event Reporting System (FAERS) data (2018Q1-2026Q2) to detect reporting anomalies and class-level spillover, and GLP1R cis–eQTL drug–target Mendelian randomization (MR) of NAION–relevant ocular phenotypes to test causal effects of GLP1R activation on semaglutide–relevant ocular toxicity.
Results
Semaglutide ROR was 116.8 (95% CI 106.8-127.7). FAERS rates rose from below 8 per 10,000 annually (2018-2023) to 52 (2024), 177 (2025), and 203 (2026H1) after July 2024 publication, while comparators remained stable. Median time to onset was 246 days (Weibull β = 1.09), a random-type profile inconsistent with cumulative toxicity. These anomalies were complemented by GLP1R–targeted MR evidence: no causal effect of genetically proxied GLP1R activation (all P ≥ 0.11), while confirming glucose–lowering ( P = 7.6E-6).
Conclusions
Pharmacovigilance and genetic evidence converge to show that the semaglutide-NAION signal reflects notoriety bias rather than toxicity.
