Semaglutide Linked to 2.3× Higher NAION (Optic Nerve) Risk vs SGLT2i in 102,000 Veterans | Research

The takeaway

Semaglutide initiators had 2.33-fold higher risk of NAION vs SGLT2i initiators (123 vs 67 per 100,000 PY) in 102,361 veterans, though the absolute risk remained low (0.29% vs 0.13%).

2.33× NAION risk
Semaglutide users had more than double the risk of this rare optic nerve condition vs SGLT2i users, though absolute risk was only 0.29%

What the researchers found

Semaglutide vs SGLT2i: NAION incidence 123 vs 67/100,000 PY; HR 2.33 (95% CI 1.54-3.54, p<0.001); absolute risk 0.29% vs 0.13%; overlap-weighted analysis of 102,361 veterans.

Why it matters

NAION causes irreversible vision loss. Even a small risk increase matters when millions take semaglutide. Clinicians should counsel patients about this rare but real risk.

How the study worked

Active-comparator new-user target trial emulation using VHA nationwide data (2018-2025), 11,478 semaglutide vs 90,883 SGLT2i initiators, overlap weighting for 95 covariates.

What this study cannot tell us

Observational design. NAION identified by codes, not ophthalmologic examination. Cannot determine causation. SGLT2i comparator may have its own NAION effects.

How to read the evidence

Large nationwide target trial emulation with active comparator and overlap weighting. Strong observational evidence.

When this study was published

Published in 2025 using VHA data through March 2025.

The bigger picture

This is the largest and most rigorous study confirming the semaglutide-NAION association, establishing it as a real but rare risk.

Questions still open

Should ophthalmologic screening be recommended for semaglutide users?
Do other GLP-1 drugs carry the same NAION risk?
What mechanism could explain semaglutide-associated NAION?

Common questions

Can semaglutide affect vision?

This large study found a rare but real increased risk of NAION, a condition causing sudden vision loss in one eye. The absolute risk is small (0.29%) but more than double the comparison group.

Should I stop semaglutide because of this?

The risk is very small (about 3 in 1,000 over 2 years), and semaglutide's cardiovascular and metabolic benefits typically far outweigh this risk. If you experience sudden vision changes, see an ophthalmologist immediately.

Read the original research

New-Onset Nonarteritic Anterior Ischemic Optic Neuropathy and Initiators of Semaglutide in US Veterans With Type 2 Diabetes.

JAMA ophthalmology

View on PubMed ↗Publisher’s paper ↗

Citation

Heberer, Kent; Bress, Adam P; Cogill, Steven; Maldonado, Ana I; Kim, Sun H; Nallamshetty, Shriram; Chen, Ying Q; Shih, Mei-Chiung; Lynch, Julie A; Lee, Jennifer S. (2026). New-Onset Nonarteritic Anterior Ischemic Optic Neuropathy and Initiators of Semaglutide in US Veterans With Type 2 Diabetes.. JAMA ophthalmology. https://doi.org/10.1001/jamaophthalmol.2025.6262