What is the risk of Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) with retatrutide (GLP-1 receptor agonist)?

NAION Risk with Retatrutide (GLP-1 Receptor Agonist)

The risk of NAION with GLP-1 receptor agonists, including retatrutide, remains uncertain but emerging evidence suggests a potential association that warrants careful monitoring, particularly in patients with pre-existing diabetic retinopathy or vascular risk factors. 1, 2

Current Evidence on GLP-1 RAs and NAION

The relationship between GLP-1 receptor agonists and NAION is evolving:

• No established causal link exists in large clinical trials. The American Heart Association notes that while PDE-5 inhibitors have been associated with NAION, the evidence shows no statistically significant increased risk (relative risk 1.02 [95% CI, 0.92 to 1.12]). 1

• Recent case reports raise concern. A 2025 case report documented NAION in a 47-year-old healthy patient treated with liraglutide and semaglutide for weight loss, with progressive visual deterioration from 20/40 to 20/400 despite continued therapy. 3

• The mechanism may be indirect. GLP-1 RAs have been associated with worsening diabetic retinopathy, particularly when there is rapid reduction in blood sugar levels rather than a direct medication effect. 2, 4

Risk Factors That Amplify NAION Concern

Patients at highest risk for NAION include those with: 5, 6

• Diabetes mellitus (present in 64.1% of NAION cases) 5
• Small cup-to-disc ratio ("disc at risk," present in 61.5% of cases) 5
• Hyperlipidemia (51.3% of cases) 5
• Hypertension (38.5% of cases) 5
• Sleep apnea syndrome 6
• Pre-existing diabetic retinopathy, especially proliferative retinopathy 4

Clinical Management Strategy

Before Starting Retatrutide:

• Obtain baseline dilated eye examination to assess for diabetic retinopathy and cup-to-disc ratio. 2, 4
• Document baseline visual acuity and visual fields if high-risk features present. 1
• Rule out other NAION risk factors including sleep apnea, carotid stenosis, and hypercoagulable states. 1

During Treatment:

• If no retinopathy present and glycemia well controlled: Screen every 1-2 years. 2, 4
• If any diabetic retinopathy present: Repeat dilated examinations at least annually. 2, 4
• If established retinopathy: Consider more gradual improvement in glycemic control to minimize rapid A1C reduction. 2, 4
• Titrate slowly to improve tolerability and potentially reduce metabolic stress. 2

If Visual Symptoms Develop:

• Immediate ophthalmologic evaluation is mandatory for any sudden painless vision loss. 3
• Rule out arteritic AION (giant cell arteritis) first - this is a true emergency requiring immediate high-dose corticosteroids. Check for temporal tenderness, jaw claudication, weight loss, proximal myalgia, or fever. 1
• Consider discontinuing GLP-1 RA therapy if NAION diagnosed, as the case report showed progression with continued use. 3
• Initiate stroke workup as NAION shares similar pathophysiology with thromboembolic events. 1

Critical Pitfalls to Avoid

• Never miss arteritic AION (GCA) - delayed corticosteroid treatment leads to irreversible bilateral blindness. 1
• Do not continue GLP-1 RA therapy if visual symptoms develop without urgent ophthalmologic evaluation. 3
• Avoid rapid glycemic improvement in patients with established retinopathy, as this appears to be the mechanism for retinal complications. 2, 4
• Do not assume absence of proven treatment means absence of need for urgent evaluation - systemic workup remains essential. 1

Age-Related Prognosis

• Younger patients (<50 years) have better outcomes: They are 2.8 times more likely to achieve final visual acuity of 20/40 or better compared to older patients (OR 2.87; 95% CI 1.12-7.40). 5
• Older patients (>50 years) have worse visual outcomes and higher prevalence of systemic vascular risk factors. 5