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. 2025 Jun;27(6):3094-3103.
doi: 10.1111/dom.16316. Epub 2025 Mar 17.

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

Emma Simonsen  1 , Lars Christian Lund  1 , Martin Thomsen Ernst  1 , Vidar Hjellvik  2 , Laszlo Hegedüs  3   4 , Steffen Hamann  5   6 , Øystein Kalsnes Jørstad  7   8 , Hanne Løvdal Gulseth  2 , Øystein Karlstad  2 , Anton Pottegård  1
Affiliations

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

Emma Simonsen et al. Diabetes Obes Metab. 2025 Jun.

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.

Keywords: SGLT2 inhibitor; antidiabetic drug; antiobesity drug; pharmaco‐epidemiology; semaglutide; type 2 diabetes.

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Conflict of interest statement

Lars Christian Lund has taught a full‐day course in epidemiological methods in drug safety surveillance at Novo Nordisk, with funds paid to the University of Southern Denmark (no personal fees). Vidar Hjellvik reports participation in research projects funded by Novo Nordisk and LEO Pharma, all regulator‐mandated phase IV studies with funds paid to the institution where he is employed (no personal fees), and with no relation to the work reported in this paper. Steffen Hamann has received grants from Rigshospitalet and the VELUX Foundation. None of these grants has any relation to the work reported in this paper. Øystein Kalsnes Jørstad has received a grant from Roche for developing an educational application. He receives royalties from SJJ Solutions for a syringe used in intravitreal injections. He has received consulting fees from SJJ Solutions and Oslo Economics. He has also received lecture fees from Allergan, Bayer, and Chiesi Farmaceutici, as well as support for meetings, travel, and attendance from SJJ Solutions. He holds patents for a needle for intravitreal injections and a glaucoma stent. Jørstad is also a member of the advisory boards for Allergan, Bayer, and Roche. None of these relationships has any relation to the work reported in this paper. Øystein Karlstad reports participation in research projects funded by Sanofi, Bristol Myers Squibb, Novo Nordisk, and LEO Pharma, all regulator‐mandated phase IV studies with funds paid to the institution where he is employed (no personal fees) and with no relation to the work reported in this paper. Anton Pottegård reports participation in research projects funded by Alcon, Almirall, Astellas, AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Servier, and LEO Pharma, all regulator‐mandated phase IV studies with funds paid to the institution where he is employed (no personal fees). Further, his research group has received one unrestricted grant from Novo Nordisk. None of these grants has any relation to the work reported in this paper. The remaining authors report no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Weighted cumulative incidence proportion of non‐arteritic anterior ischemic optic neuropathy outcomes with 95% confidence intervals (grey area) over time since the initiation of semaglutide and sodium‐glucose co‐transporter 2 inhibitors in Denmark (top panel) and Norway (bottom panel).
See this image and copyright information in PMC

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