Optic Ischaemic Neuropathy in Incretin-Based Therapy: A Comparative Analysis of Real-World Safety Data

Non-arteritic anterior ischemic optic neuropathy (NAION) has emerged as a safety concern with semaglutide, prompting formal regulatory review and action by the European Medicines Agency. However, its occurrence across the broader class of incretin-based therapies is insufficiently characterised. This study used the FDA Adverse Event Reporting System to evaluate and compare pharmacovigilance signals for optic ischaemic neuropathy across six incretin-based therapies.

Adverse event reports from each drug's approval date through Q3 2025 were extracted using OpenVigil 2.1. The Medical Dictionary for Regulatory Activities term "optic ischaemic neuropathy" was used as the outcome. Disproportionality analysis was performed using reporting odds ratio (ROR) and proportional reporting ratio (PRR) with 95% confidence intervals, applying Evans' criteria, restricted to primary suspect drug reports.

Semaglutide demonstrated a strong post-marketing safety signal for optic ischaemic neuropathy (355 reports; ROR 94.45, 95% CI: 83.02-107.45; PRR 93.77, 95% CI: 82.48-106.61). Tirzepatide and liraglutide also exhibited significant safety signals (49 reports; ROR 2.94, 95% CI: 2.20-3.93; PRR 2.94, 95% CI: 2.20-3.93; and 13 reports; ROR 4.58, 95% CI: 2.65-7.91; PRR 4.58, 95% CI: 2.65-7.91, respectively). No signal was identified for dulaglutide, exenatide, or lixisenatide. Among semaglutide-associated reports, mean age was 59 years; disability was documented in 18% and hospitalization in 11% of cases.

Significant post-marketing safety signals for optic ischaemic neuropathy were identified for semaglutide, tirzepatide, and liraglutide. The absence of signals with other glucagon-like peptide-1 receptor agonists argues against a uniform class effect. Prospective studies with neuro-ophthalmologist-confirmed diagnoses are warranted to establish causality and quantify absolute risk.