Large Danish-Norwegian study confirms semaglutide increases risk of rare eye condition NAION by nearly 3-fold | Research

The takeaway

In 61,377 diabetic patients, semaglutide was associated with a 2.81-fold increased risk of non-arteritic anterior ischemic optic neuropathy (NAION) versus SGLT2i, with an absolute risk increase of 1.41 per 10,000 person-years.

HR 2.81 for NAION
Semaglutide nearly triples the risk of sudden optic nerve damage (NAION) versus SGLT2i, though absolute risk remains about 1.4 additional cases per 10,000 patient-years

What the researchers found

Pooled HR 2.81 (95% CI 1.67-4.75). Denmark HR 2.17 (1.20-3.92), Norway HR 7.25 (2.34-22.4). IRD +1.41/10,000 person-years. Per-protocol HR 6.35 (2.88-14.0). 32 NAION events total. Consistent across sensitivity analyses.

Why it matters

NAION causes sudden, irreversible vision loss. This is the largest and most rigorous study confirming the association with semaglutide, providing critical safety information for millions of users.

How the study worked

Population-based cohort study using national health registries in Denmark (2018-2024) and Norway (2018-2022). Active comparator (SGLT2i). Fixed-effects meta-analysis pooling. Self-controlled supplementary analysis.

What this study cannot tell us

Observational study—cannot prove causation. Active comparator design (vs SGLT2i) may inflate or deflate relative risk. NAION events rare (32 total). Norwegian estimates less precise. Potential for residual confounding.

How to read the evidence

Large population-based cohort with active comparator design, multi-country replication, and extensive sensitivity analyses. Strong observational evidence.

When this study was published

Published in 2025; largest study to date on semaglutide-NAION association.

The bigger picture

This adds to the growing safety profile of semaglutide. While the absolute risk is low, the relative risk increase is substantial. Clinicians must weigh this against semaglutide's proven mortality and cardiovascular benefits.

Questions still open

Does the NAION risk apply to all GLP-1 agonists or just semaglutide?
Is the risk dose-dependent?
Should patients with NAION risk factors avoid semaglutide?

Common questions

Can semaglutide cause vision loss?

This large study found semaglutide nearly triples the risk of NAION—a condition causing sudden, painless vision loss from optic nerve damage. However, the absolute risk is very low: about 2 cases per 10,000 patient-years versus less than 1 with SGLT2 inhibitors. Most semaglutide users will not experience this.

Should I stop semaglutide because of this?

Not necessarily. The overall benefits of semaglutide (15% mortality reduction, cardiovascular protection) likely outweigh this small risk for most patients. However, if you experience sudden vision changes, seek immediate eye care. Discuss your personal risk factors with your doctor.

Read the original research

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

Diabetes, obesity & metabolism, 27(6), 3094-3103

View on PubMed ↗Publisher’s paper ↗

Citation

Simonsen, Emma; Lund, Lars Christian; Ernst, Martin Thomsen; Hjellvik, Vidar; Hegedüs, Laszlo; Hamann, Steffen; Jørstad, Øystein Kalsnes; Gulseth, Hanne Løvdal; Karlstad, Øystein; Pottegård, Anton. (2025). Use of semaglutide and risk of non-arteritic anterior ischemic optic neuropathy: A Danish-Norwegian cohort study.. Diabetes, obesity & metabolism, 27(6), 3094-3103. https://doi.org/10.1111/dom.16316