Association between Semaglutide and Non-Arteritic Anterior Ischemic Optic Neuropathy: A Multinational Population-Based Real-World Study

Abstract

ObjectiveTo investigate whether semaglutide increases the risk of non-arteritic anterior ischemic optic neuropathy (NAION) in the general population. DesignThis retrospective cohort study utilized a de-identified global electronic medical records database. The enrollment period was extended from January 2017 to August 2023, with observations concluding in August 2024. ParticipantsThis study included individuals with type 2 diabetes mellitus (T2DM) or obesity. They were further categorized into T2DM-only, obesity-only, and T2DM with obesity groups to assess the differences among these subgroups. The effects of semaglutide were compared with those of glucose-lowering or weight loss medications other than glucagon-like peptide receptor agonists. MethodsPatient data were obtained from 160 healthcare organizations across 21 countries. Outcomes were evaluated at one, two, and three years of follow-up. A 1:1 propensity score matching was performed to balance age, sex, body mass index, hemoglobin A1C, medications, and underlying comorbidities. Cox regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI). Main Outcome MeasuresThe occurrence of NAION. ResultsThe final analysis included 37,245 participants with T2DM-only, 33,537 participants with obesity-only, and 64,989 participants with both T2DM and obesity. The results indicated that the administration of semaglutide was not associated with the development of NAION in the T2DM-only group (1 year follow-up: HR, 2.32; 95% CI, 0.60–8.97; 2 years: HR, 2.31; 95% CI, 0.86–6.17; 3 years: HR, 1.51; 95% CI, 0.71–3.25), the obesity-only group (1 year follow-up: HR, 0.25; 95% CI, 0.03–2.28; 2 years: HR, 0.44; 95% CI, 0.09–2.21; 3 years: HR, 0.44; 95% CI, 0.09–2.21), and the T2DM with obesity group (1 year follow-up: HR, 0.81; 95% CI, 0.42–1.57; 2 years: HR, 1.2; 95% CI, 0.74–1.94; 3 years: HR, 1.19; 95% CI, 0.78–1.82). ConclusionsThe findings suggest that semaglutide may not be associated with an increased risk of NAION in the general population. Therefore, avoidance of semaglutide based solely on concerns regarding the risk of NAION may not be warranted, as its potential benefits for blood glucose control and cardiovascular health likely outweigh its potential risks.