Use of semaglutide and risk of non‐arteritic anterior ischemic optic neuropathy: A Danish–Norwegian cohort study

Abstract Aims To investigate the putative association between semaglutide and non‐arteritic anterior ischaemic optic neuropathy (NAION). Materials and Methods Data from national health registries in Denmark (2018–2024) and Norway (2018–2022) were used to compare NAION risk in individuals with type 2 diabetes initiating semaglutide versus sodium‐glucose co‐transporter 2 inhibitors (SGLT‐2is). A supplementary self‐controlled analysis examined NAION risk among all semaglutide users. National estimates were pooled using a fixed‐effects model. Results We identified 44 517 users of semaglutide for the management of type 2 diabetes in Denmark and 16 860 in Norway, with a total of 32 NAION events observed. The unadjusted incidence rate of NAION was 2.19/10 000 person‐years among Danish semaglutide initiators, compared to 1.18 among SGLT‐2i initiators. In Norway, the corresponding rates were 2.90 and 0.92, respectively. After adjustment, the pooled hazard ratio (HR) was 2.81 (95% confidence interval [CI] 1.67–4.75), and the incidence rate difference (IRD) was +1.41 (95% CI +0.53 to +2.29) per 10 000 person‐years. Estimates were consistent across both countries but higher and less precise in Norway (HR 7.25; 95% CI 2.34–22.4) compared to Denmark (HR 2.17; 95% CI 1.20–3.92). Results remained consistent across sensitivity and supplementary analyses, with a stronger association observed in a post hoc per‐protocol analysis (HR 6.35; 95% CI 2.88–14.0). In the supplementary self‐controlled study, symmetry ratios (SRs) for NAION were 1.14 (95% CI 0.55–2.36) in Denmark and 2.67 (95% CI 0.91–8.99) in Norway. Conclusions The use of semaglutide for managing type 2 diabetes is associated with an increased risk of NAION compared with the use of SGLT‐2is. However, the absolute risk remains low.