Semaglutide and risk of Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) in type 2 diabetes mellitus: A systematic review and meta-analysis

Published May 27, 2026Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie

Semaglutide and the risk of sudden optic nerve damage in type 2 diabetes: A systematic review and meta-analysis

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GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗

Page updated Jun 27, 2026

Abstract

Essence

Semaglutide use in type 2 diabetes was associated with higher NAION risk than non-GLP-1RA treatment.

Evidence

This systematic review and meta-analysis included 12 studies and pooled eight retrospective cohorts with 14,255,247 participants, reporting HR 3.36 at 1 year, HR 2.37 at 2 years, HR 2.37 at 3 years after sensitivity analysis, and HR 2.37 at 5 years.

Caveat

The evidence is observational with very high 1-year heterogeneity and relies on retrospective cohort comparisons rather than randomized assignment.

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BACKGROUND: The use of Glucagon-like peptide-1 receptor agonists (GLP-1RAs) has expanded dramatically worldwide, with semaglutide being one of the most widely utilized agents. Nonarteritic anterior ischemic optic neuropathy (NAION) has been associated with GLP-1RAs use from emerging pharmacovigilance data. This systematic review and meta-analysis sought to evaluate the risk of NAION in patients with type 2 diabetes mellitus (T2DM).

METHODS: A literature search was made up to September 2025 (PROSPERO: CRD420251155026). Results were synthesized following the PRISMA guidelines and are presented as pooled Hazard Ratios (HR) with 95% confidence intervals (CI).

RESULTS: Twelve studies were included; eight retrospective cohorts (14,255,247 participants) were meta-analyzed, with a mean age of 59.3 ± 15.9 years and 32.7% males. Patients with T2DM using semaglutide compared to non-GLP-1RAs showed an increased risk of NAION at 1-year follow-up with a pooled HR of 3.36 (95% CI: 1.44-7.84; p < 0.001; I = 97%). At 2-year follow-up, the pooled HR was 2.37 (95% CI: 1.46-3.85; p < 0.001; I² = 0%). The 3-year risk after the sensitivity analysis showed a pooled HR of 2.37 (95% CI: 1.45-3.87, p < 0.001; I² = 28%), and the 5-year pooled HR was 2.37 (95% CI: 0.62-3.92; p < 0.001; I² = 0%). 2

CONCLUSION: This meta-analysis indicates a significant association between semaglutide use and NAION in patients with T2DM compared to non-GLP-1RAs, with this association remaining significant even after 5-years of semaglutide use.