GLP-1 RAs and NAION: What Optometrists Need to Know Right Now

NAION is the most common acute optic neuropathy in adults over 50, with an annual incidence of roughly 2–10 per 100,000.¹ It presents as painless, usually unilateral, with sudden visual loss, typically altitudinal field defect, often noticed on wakening, caused by ischaemia of the optic nerve head. Visual recovery is limited, and there is no proven treatment. The fellow eye will subsequently become involved in up to 30% of cases.²

Several ocular and systemic risk factors have been associated with NAION. These include a structurally small disc-at-risk (crowded optic disc), diabetes mellitus, hypertension, dyslipidaemia, obstructive sleep apnoea, and nocturnal hypotension.

Many patients taking GLP-1 RAs have these exact vascular risk factors, which is important to note as this confounds interpreting the literature.

These are striking numbers, but the study had some important limitations… More than a dozen studies have rapidly followed. The picture that has emerged is mixed”

How the Signal Emerged

The headline study was published by Hathaway et al. in JAMA Ophthalmology in July 2024.³ Clinicians at the Massachusetts Eye and Ear noticed anecdotal cases of NAION occurring in patients taking semaglutide. They conducted a retrospective cohort study and compared semaglutide users with matched controls. Of 710 patients with type 2 diabetes, NAION occurred in 17 of 194 semaglutide users (8.9%) versus six of 516 controls (1.8%), representing a hazard ratio (HR) of 4.3 (95% CI 1.6–11.3). Among 979 patients taking it for obesity, 20 of 361 semaglutide users developed NAION versus three of 618 controls (HR 7.6, 95% CI 2.2–26.4).

These are striking numbers, but the study had some important limitations. Apart from its small sample size, as reflected by the wide confidence intervals, the study was conducted at a single tertiary neuro-ophthalmology referral centre and was thus prone to selection and referral bias.

More than a dozen studies have rapidly followed. The picture that has emerged is mixed.

The Evolving Evidence

Studies Reporting Elevated Risk

Scandinavian registry data reports increased risk. Simonsen et al., using Danish and Norwegian national health registries, reported a HR of approximately 2.8 for NAION in new semaglutide users versus SGLT2 inhibitor users⁴ (SGLT2 inhibitors are a class of prescription medications that block the sodium-glucose co-transporter 2 protein).Grauslund et al., in a prospective nationwide Danish cohort of over 424,000 patients with type 2 diabetes, found semaglutide approximately doubled the five-year risk of NAION.⁵ A recent US study by Tesfaye et al. involved three large insurance databases. They found that initiation of a GLP-1 RA was associated with a HR of 1.85 (95% CI 1.51–2.27) for presumed NAION.⁶

Studies Reporting No Significant Increase

Counterbalancing these, several large studies have not found elevated risk. Chou et al. in a multinational cohort of just under 300,000 patients across 21 countries drawn from the TriNetX network, found no increased NAION risk in semaglutide users over three years.⁷

In the largest study to date of more than 2.4 million patients with type 2 diabetes, Bartelt et al. reported semaglutide and dulaglutide were not associated with an increased risk of NAION, while liraglutide and insulin showed an association with elevated risk, which may have been confounded by disease severity.⁸

Meta-Analyses of Randomised Controlled Trials

Meta-analyses pool available studies together to increase statistical power to infer causation that single trials may not be able to do with rare events such as NAION. Natividade et al. focused on semaglutide and found no increase in overall eye disorders or diabetic retinopathy but did see a signal for NAION (OR approx. 3.9, 95% CI 1.02–15.02).⁹ The authors concluded the evidence was still too limited and insufficiently powered to be definitive.

Silverii et al. looked at the broader GLP-1 RA class and found no statistically significant increase in NAION, and that there were a very small number of events.¹⁰

The Regulatory Response

In July 2026, Australia’s Therapeutic Goods Administration issued a medicine safety update. They notified prescribers that product warnings across the GLP-1 RA class of medicines had been updated due the potential for these medications to cause a NAION.¹¹ The update is notable as regulatory action reflects a plausible signal, even when causation remains unproven.

Causation Remains Unresolved

A comprehensive 2026 review in Clinical and Experimental Ophthalmology by Danesh-Meyer and Rizzo carefully assessed the hierarchy of evidence, from case series through to meta-analyses of randomised control trials (RCTs).¹² Their analysis highlights a fundamental challenge: NAION lacks its own ICD-10 code (a globally standardised diagnostic coding system), making administrative dataset identification unreliable. Differences between study populations, comparator groups, and analytical methods all contribute to divergent findings. Danesh-Meyer and Rizzo concluded that even if GLP-1 RAs were ultimately shown to double the relative risk of NAION, the absolute lifetime excess risk would be outweighed by the well-established cardiovascular benefits of these drugs.¹²

RANZCO does not recommend routinely stopping GLP-1 agents based on current evidence.

RANZCO’s Position

The Royal Australian and New Zealand College of Ophthalmologists (RANZCO) has issued a position statement¹³ acknowledging the potential association while emphasising that causation has not been established. RANZCO does not recommend routinely stopping GLP-1 agents based on current evidence. Patients with prior NAION, marked optic-disc crowding, or multiple vascular risk factors may be at higher risk for fellow-eye involvement and should be discussed individually.

The Optometrist’s Role: Be Aware, Not Alarmed

When a patient mentions they are taking a GLP-1 RA, consider the following:

• Document GLP-1 RA use in the medication history alongside noting other NAION risk factors.
• Assess the optic disc for a disc-at-risk appearance – a small disc with little or no physiological cup, often described as a ‘crowded’ nerve. This is the most consistently validated anatomical risk factor for NAION.
• Note disc drusen, as these may further compromise optic nerve head vasculature and represent an added risk in susceptible individuals.
• Assess and note systemic vascular risk factors – blood pressure control, dyslipidaemia, HbA1c, and sleep apnoea history.
• Consider referral to an ophthalmologist for individualised risk-benefit assessment for patients starting GLP-1 RAs who have multiple NAION risk factors, particularly a disc-at-risk or prior NAION in the fellow eye.
• Advise patients to seek same-day assessment for sudden painless vision loss, a new scotoma or field defect.
• Do not advise patients to stop their GLP-1 RA without discussion with their prescribing physician – these drugs carry major cardiovascular and metabolic benefits.

What Patients Are Asking

In practice, patients are increasingly aware of the NAION story. Some have read about United States litigation (legal proceedings involving GLP-1 RAs and NAION are ongoing in the US) and arrive anxious about their medication.

As eye care professionals, our role is to provide balanced information: the signal exists and is being taken seriously, however the absolute risk remains low and causation remains unproven.

The link between the two is complex because it is hard to separate the risk of GLP-1 RAs from cardiovascular risk factors when it comes to NAION. GLP-1 RAs can also help with vascular risk factor reduction. Stopping medication without medical advice is not recommended. A discussion involving the GP, physician, ophthalmologist, and patient should take place so patients can make an informed decision.

Looking Ahead

Larger pooled analyses of RCTs may definitively answer the causation question. Until then, the current position is of informed vigilance rather than of alarm.

 

Dr Yen Cheng BMedSc MBBS MMed (OphthSc) FRANZCO is an ophthalmologist with subspecialties in glaucoma and cataract surgery. She is a certified minimally invasive glaucoma surgery (MIGS) specialist. Dr Cheng is an investigator in the development of nanoparticle-based therapeutics for glaucoma neuroprotection and wound healing, and supervises clinical and research students from the University of Sydney.

References

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2. Miller NR, Arnold AC. Current concepts in the diagnosis, pathogenesis and management of nonarteritic anterior ischaemic optic neuropathy. Eye (Lond). 2015 Jan;29(1):65-79. doi: 10.1038/eye.2014.144.
3. Hathaway JT, Shah MP, Rizzo JF 3rd, et al. Risk of nonarteritic anterior ischemic optic neuropathy in patients prescribed semaglutide. JAMA Ophthalmol. 2024 Aug 1;142(8):732-739. doi: 10.1001/jamaophthalmol.2024.2296.
4. Simonsen E, Lund LC, Pottegård A, at al. Use of semaglutide and risk of non-arteritic anterior ischemic optic neuropathy: A Danish-Norwegian cohort study. Diabetes Obes Metab. 2025 Jun;27(6):3094-3103. doi: 10.1111/dom.16316.
5. Grauslund J, Taha AA, Stokholm L, et al. Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes. Int J Retina Vitreous. 2024 Dec 18;10(1):97. doi: 10.1186/s40942-024-00620-x.
6. Tesfaye H, Paik JM, Patorno E, et al. GLP-1RA and the risk of non-arteritic anterior ischaemic optic neuropathy in patients with type 2 diabetes: A population-based study. Diabetes Obes Metab. 2026 Feb;28(2):1517-1528. doi: 10.1111/dom.70200.
7. Chou CC, Pan SY, Weng CH, et al. Association between semaglutide and nonarteritic anterior ischemic optic neuropathy: A multinational population-based study. Ophthalmology. 2025 Apr;132(4):381-388. doi: 10.1016/j.ophtha.2024.10.030.
8. Bartelt K, Swaminathan S, Deckert J, et al. Liraglutide and insulin prescriptions associated with increased likelihood of rare vision loss. Epic Research. Available at: epicresearch.org/articles/liraglutide-and-insulin-prescriptions-associated-with-increased-likelihood-of-rare-vision-loss. [Accessed July 2026].
9. Natividade GR, Spiazzi BF, Gerchman F, et al. Ocular adverse events with semaglutide: A systematic review and meta-analysis. JAMA Ophthalmol. 2025 Sep 1;143(9):759-768. doi: 10.1001/jamaophthalmol.2025.2489.
10. Silverii GA, Pala L, Cresci B, Mannucci E. Glucagon-like peptide 1 (GLP1) receptor agonists and risk for ischemic optic neuropathy: A meta-analysis of randomised controlled trials. Diabetes Obes Metab. 2025 Feb;27(2):1005-1009. doi: 10.1111/dom.16076.
11. Therapeutic Goods Administration, GLP-1 RAs and rare vision disorder, Medicine Safety Update, 23 July 2016, available at: tga.gov.au/news/safety-updates/glp-1-ras-and-rare-vision-disorder [accessed August 2026].
12. Danesh-Meyer HV, Rizzo JF III. Is there a causal link between GLP-1 receptor agonists and NAION? A critique of the clinical evidence. Clin Exp Ophthalmol. 2026. doi: 10.1111/ceo.70096.
13. Royal Australian and New Zealand College of Ophthalmologists, RANZCO Position Statement: GLP-1 Receptor agonists and non-arteritic anterior ischaemic optic neuropathy (NAION) March 2026. Available at ranzco.edu/wp-content/uploads/2026/04/RANZCO-Position-Statement-GLP1-Receptor-Agonists-and-Non-Arteritc-Anterior-Ischaemic-Optic-Neuropathy-NAION.pdf [accessed Jul 2026].