Objective:

To evaluate the long-term risk of nonarteritic anterior ischemic optic neuropathy (NAION) in patients with diabetes receiving semaglutide compared to those on non-GLP-1 RA antidiabetic medications.

Key Findings:

• Semaglutide use was not associated with a statistically significant increase in NAION risk through 1 year of follow-up.
• Elevated relative risk of NAION emerged at 2 years and persisted through 4 years.
• NAION occurred in 45 semaglutide-treated patients (0.026%) compared to 29 patients on non-GLP-1 RA therapies (0.017%).
• Hazard ratio for NAION with semaglutide was 2.22 compared to non-GLP-1 RA use, indicating approximately twice the risk.
• Increased risk observed in patients aged 40-64, female patients, White patients, and those with hypertension.

Interpretation:

The study suggests an elevated risk of NAION associated with semaglutide use in diabetic patients, particularly in specific subgroups, but findings are preliminary and require further investigation through well-designed studies.

Limitations:

• Retrospective observational design limits causal inference.
• Inability to verify medication adherence and potential residual confounding.
• ICD-10 diagnostic code for NAION may not be fully specific, risking outcome misclassification.
• Small event counts in subgroup analyses limit the robustness of findings.

Conclusion:

The study indicates an association between semaglutide use and increased NAION risk in diabetic patients, warranting further observational studies to confirm these findings.