Semaglutide, Tirzepatide, and Liraglutide Linked to Optic Ischaemic Neuropathy Signals in Real-World Data
Background
Non-arteritic anterior ischemic optic neuropathy (NAION) has emerged as a serious safety concern with semaglutide, prompting formal regulatory review by the European Medicines Agency. This condition involves sudden vision loss due to impaired blood flow to the optic nerve. While the risk with semaglutide is under scrutiny, the broader impact across the class of incretin-based therapies remains poorly characterized. Understanding whether this is a class effect or specific to certain compounds is crucial for patient safety and clinical decision-making, addressing a critical gap in pharmacovigilance.
Study Design
Researchers conducted a comparative pharmacovigilance study using the FDA Adverse Event Reporting System (FAERS). Adverse event reports for six incretin-based therapies—semaglutide, tirzepatide, liraglutide, dulaglutide, exenatide, and lixisenatide—were extracted from their respective approval dates through Q3 2025 via OpenVigil 2.1. The primary outcome was optic ischaemic neuropathy, identified using the Medical Dictionary for Regulatory Activities (MedDRA) term. 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.
Results
Significant post-marketing safety signals for optic ischaemic neuropathy were identified for three incretin-based therapies. Semaglutide demonstrated a strong signal with 355 reports (ROR 94.45, 95% CI: 83.02-107.45; PRR 93.77, 95% CI: 82.48-106.61). Tirzepatide also exhibited a significant signal with 49 reports (ROR 2.94, 95% CI: 2.20-3.93; PRR 2.94, 95% CI: 2.20-3.93), as did liraglutide with 13 reports (ROR 4.58, 95% CI: 2.65-7.91; PRR 4.58, 95% CI: 2.65-7.91). In contrast, no safety signal was identified for dulaglutide, exenatide, or lixisenatide. Among the semaglutide-associated reports, the mean age of affected individuals was 59 years, with disability documented in 18% of cases and hospitalization in 11%. These findings suggest a differential risk profile within the incretin class.
Semaglutide showed the strongest signal for optic ischaemic neuropathy, with a Reporting Odds Ratio of 94.45, indicating a vastly disproportionate number of reports compared to other drugs.
Key Findings
- Semaglutide showed a strong safety signal for optic ischaemic neuropathy with 355 reports (ROR 94.45).
- Tirzepatide exhibited a significant signal with 49 reports (ROR 2.94).
- Liraglutide also had a significant signal with 13 reports (ROR 4.58).
- No safety signal was identified for dulaglutide, exenatide, or lixisenatide.
- Among semaglutide reports, mean age was 59 years, with 18% disability and 11% hospitalization.
Why It Matters
This study provides crucial real-world safety data, indicating that the risk of optic ischaemic neuropathy is not a uniform class effect across all incretin-based therapies. Clinicians and patients using semaglutide, tirzepatide, or liraglutide should be vigilant for visual disturbances and report any new symptoms promptly. For individuals experiencing this adverse event, the absence of signals with dulaglutide, exenatide, or lixisenatide suggests that switching to a different GLP-1 receptor agonist might be a safer alternative, though this requires further clinical validation. This information is vital for informed prescribing and patient counseling, especially given the widespread use of these medications for type 2 diabetes and obesity. The findings underscore the need for prospective studies with neuro-ophthalmologist-confirmed diagnoses to establish causality and quantify absolute risk, moving beyond spontaneous reports to more definitive clinical guidance.
semaglutide
tirzepatide
liraglutide
optic-neuropathy
adverse-event
pharmacovigilance