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

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.