NAION Risk with Ozempic (Semaglutide)
Emerging evidence suggests semaglutide is associated with an increased risk of non-arteritic anterior ischemic optic neuropathy (NAION), with recent data showing a 4-7 fold increased hazard ratio compared to other diabetes and weight-loss medications.
Evidence of Association
The most robust evidence comes from a 2024 retrospective cohort study that demonstrated:
In patients with type 2 diabetes: Semaglutide showed a hazard ratio of 4.28 (95% CI, 1.62-11.29) for NAION, with cumulative incidence of 8.9% over 36 months versus 1.8% in non-GLP-1 RA users 1
In overweight/obese patients: Even higher risk with hazard ratio of 7.64 (95% CI, 2.21-26.36), with cumulative incidence of 6.7% over 36 months versus 0.8% in non-GLP-1 RA users 1
Multiple case reports from 2025-2026 corroborate this association, with NAION developing within months of semaglutide initiation 2, 3, 4, 5. One particularly concerning case involved an otherwise healthy 47-year-old with no diabetes or hypertension who developed progressive NAION leading to 20/400 vision after starting liraglutide followed by semaglutide for weight loss 5.
Clinical Presentation and Risk Factors
Patients who developed NAION on semaglutide typically presented with:
- Sudden, painless vision loss occurring within 1-4 months of therapy initiation 2, 3, 4
- Significant optic disc edema confirmed on optical coherence tomography 2, 3, 4
- Anatomical predisposition: Small Bruch's membrane opening diameter (<1.4 mm) and crowded optic discs appear to increase susceptibility 3
- Visual field defects corresponding to ganglion cell layer atrophy 3
Critical Clinical Recommendations
Before initiating semaglutide:
- Ensure comprehensive ophthalmologic examination has been completed within the past 12 months, particularly if rapid glucose reduction is anticipated 6
- Assess for anatomical risk factors including crowded optic discs and small cup-to-disc ratios 3
- Document baseline visual acuity and visual fields in high-risk patients 5
During semaglutide therapy:
- Immediately discontinue semaglutide if any visual symptoms develop, as continued use may worsen outcomes 5
- Arrange urgent ophthalmology evaluation for any patient reporting vision changes 5
- Consider more frequent monitoring in patients with pre-existing vascular risk factors or anatomical predisposition 2, 3
Important Context from Established Guidelines
While the American College of Cardiology guidelines note that semaglutide was associated with increased diabetic retinopathy complications in SUSTAIN-6 (hypothesized to relate to rapid glucose reduction), they recommend eye examinations before starting therapy 6. However, these guidelines predate the emerging NAION data and focused on retinopathy rather than optic neuropathy 6.
The American Academy of Ophthalmology notes that PDE-5 inhibitors have been associated with NAION but showed no statistically significant increased risk (RR 1.02), making the 4-7 fold increased risk with semaglutide substantially more concerning 7.
Key Pitfalls to Avoid
- Do not confuse NAION with arteritic AION: Rule out giant cell arteritis (temporal tenderness, jaw claudication, elevated ESR/CRP) which requires immediate high-dose corticosteroids to prevent bilateral blindness 7, 8
- Do not continue semaglutide after visual symptoms develop: Case reports show progressive deterioration with continued use 5
- Do not assume only diabetic patients are at risk: The hazard ratio was actually higher in overweight/obese patients without diabetes 1
- Do not delay ophthalmology referral: Early diagnosis and treatment interruption are essential to prevent severe visual morbidity 5
Mechanism and Pathophysiology
The exact mechanism remains unclear but may involve: