Does Semaglutide Cause Eye Problems? A Major Meta-Analysis of 78 Trials Weighs In | Research

The takeaway

Semaglutide was not associated with increased risk of general eye disorders or diabetic retinopathy across 78 trials with 73,640 participants, but a nearly fourfold increase in odds of a rare optic nerve condition (NAION) was observed, though evidence remains insufficient for definitive conclusions.

OR 3.92 for NAION
Semaglutide was associated with nearly fourfold increased odds of nonarteritic anterior ischemic optic neuropathy, a rare condition affecting the optic nerve, though evidence remains insufficient for definitive conclusions.

What the researchers found

Across 78 randomized clinical trials with 73,640 participants, semaglutide showed no association with increased risk of eye disorders overall (OR 1.01; 95% CI 0.91–1.12) or diabetic retinopathy specifically (OR 1.04; 95% CI 0.92–1.17).

However, semaglutide treatment was associated with significantly increased odds of nonarteritic anterior ischemic optic neuropathy (NAION), with an OR of 3.92 (95% CI 1.02–15.02). This is a rare but serious condition involving sudden loss of blood flow to the optic nerve.

Trial sequential analysis confirmed sufficient sample size to rule out increased diabetic retinopathy risk, but the data were insufficient to draw definitive conclusions about the NAION association, given the rarity of this event.

Why it matters

Semaglutide is one of the most widely prescribed medications in the world. Early reports of potential eye problems alarmed patients and clinicians alike. This meta-analysis provides the most comprehensive safety assessment to date, reassuring patients about general eye health and diabetic retinopathy while flagging a potential rare risk (NAION) that deserves monitoring and further study.

How the study worked

The researchers conducted a systematic review and meta-analysis following standard methodology. They searched PubMed, Embase, and Cochrane Central Register through April 2025 with no date restrictions. Only randomized clinical trials comparing semaglutide to active comparators or placebo in adults were included. They used random-effects models for eye disorders and diabetic retinopathy, Peto OR with fixed effects for the rare NAION outcome, assessed bias with RoB 2.0, graded evidence quality with GRADE, and performed trial sequential analysis to evaluate data sufficiency.

What this study cannot tell us

The NAION finding, while statistically significant, has a very wide confidence interval (1.02–15.02) suggesting imprecision. Trial sequential analysis confirmed the data were insufficient for definitive NAION conclusions. The meta-analysis relied on adverse event reporting from trials not specifically designed to detect ocular outcomes, which may lead to underreporting. Individual trial definitions of ocular adverse events may have varied.

How to read the evidence

This is a systematic review and meta-analysis of 78 randomized clinical trials — the highest tier of evidence. Published in JAMA Ophthalmology with rigorous methodology including GRADE assessment and trial sequential analysis. Risk of bias across included studies was rated low.

When this study was published

Published in 2025 with literature searched through April 2025, this is among the most current and comprehensive assessments of semaglutide ocular safety available.

The bigger picture

This meta-analysis addresses one of the most high-profile safety questions surrounding GLP-1 receptor agonists. The NAION signal, while statistically significant, illustrates the challenge of detecting rare adverse events even in large datasets. As semaglutide use expands globally, pharmacovigilance systems and real-world evidence studies will be essential for monitoring this and other uncommon risks that clinical trials may not be powered to definitively assess.

Questions still open

What is the absolute risk of NAION in semaglutide users versus the general population, and does it vary by dose or duration?
Do other GLP-1 receptor agonists like liraglutide or tirzepatide carry a similar NAION risk signal?
Should patients with pre-existing optic nerve conditions be screened before starting semaglutide therapy?

Common questions

Should I worry about my eyes if I'm taking semaglutide?

This large analysis found no increased risk of general eye problems or diabetic retinopathy with semaglutide. There was a signal for a very rare optic nerve condition (NAION), but the evidence isn't strong enough for definitive conclusions. If you experience sudden vision changes, contact your doctor promptly, as you would with any medication.

What is NAION and how common is it?

NAION (nonarteritic anterior ischemic optic neuropathy) is a rare condition where blood flow to the optic nerve is suddenly reduced, which can cause painless vision loss. It affects roughly 2-10 per 100,000 people per year in the general population. Even with the elevated odds ratio found in this study, it remains a rare event.

Read the original research

Ocular Adverse Events With Semaglutide: A Systematic Review and Meta-Analysis.

JAMA ophthalmology, 143(9), 759-768

View on PubMed ↗Publisher’s paper ↗

Citation

Natividade, Gabriella R; Spiazzi, Bernardo F; Baumgarten, Matheus W; Bassotto, Caroline; Pereira, Afonso A; Fraga, Bruna L; Scalco, Bruno G; Mattes, Nicole R; Lavinsky, Daniel; Kramer, Caroline K; Gerchman, Fernando. (2025). Ocular Adverse Events With Semaglutide: A Systematic Review and Meta-Analysis.. JAMA ophthalmology, 143(9), 759-768. https://doi.org/10.1001/jamaophthalmol.2025.2489