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Background <p>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).</p> Methods <p>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).</p> Results <p>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; <i>p</i> &lt; 0.001; I<sup>2</sup> = 97%). At 2-year follow-up, the pooled HR was 2.37 (95% CI: 1.46–3.85; <i>p</i> &lt; 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, <i>p</i> &lt; 0.001; I² = 28%), and the 5-year pooled HR was 2.37 (95% CI: 0.62–3.92; <i>p</i> &lt; 0.001; I² = 0%).</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 发表日期：

    2026年5月27日

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  • Stamatios Lampsas,
  • Chrysa Agapitou,
  • Evangelos Oikonomou,
  • Gerasimos Siasos,
  • Panagiotis Theodossiadis,
  • Georgios Tsivgoulis,
  • Vaia Lambadiari,
  • Irini Chatziralli

摘要

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; I2 = 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%).

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.