Can patients with Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) use Mounjaro (tirzepatide) for type 2 diabetes?

Can Patients with NAION Use Mounjaro (Tirzepatide)?

Patients with established NAION can use Mounjaro (tirzepatide), but clinicians must carefully weigh the cardiovascular and metabolic benefits against the theoretical risk of worsening optic neuropathy, particularly given the emerging but controversial association between GLP-1 receptor agonists and NAION. 1, 2

Current Evidence on GLP-1 Receptor Agonists and NAION

The relationship between GLP-1 receptor agonists (like tirzepatide, which has dual GLP-1/GIP activity) and NAION remains highly controversial:

• No established causal relationship exists. Clinical trials of semaglutide (a pure GLP-1RA) did not report significant increases in NAION risk 1, 2
• A recent retrospective cohort study suggested a possible association between GLP-1RAs and NAION, sparking debate 1, 2
• Subsequent studies have shown conflicting results, with no consensus on causality 1
• Very low-quality evidence exists regarding any association between similar medications (PDE-5 inhibitors) and NAION 3

Risk Factors to Consider in NAION Patients

Patients with NAION typically have multiple vascular risk factors that require aggressive management:

• Diabetes is present in 64.1% of NAION patients and is a major risk factor 4
• Hypertension (38.5%), hyperlipidemia (51.3%), and obesity are highly prevalent 4
• NAION shares similar pathophysiology with other thromboembolic events 5
• Diabetic patients with NAION show longer optic disc edema resolution times but similar visual outcomes compared to non-diabetics 6

Clinical Decision-Making Algorithm

For patients with established NAION and type 2 diabetes:

1. Prioritize cardiovascular risk reduction. GLP-1RAs (and by extension, tirzepatide) reduce major adverse cardiovascular events in patients with type 2 diabetes and established cardiovascular disease 7

2. Optimize all vascular risk factors aggressively:

   • Achieve near-normal glycemic control (HbA1c <7%) to prevent diabetic complications including neuropathy 7, 8
   • Manage hypertension and lipids intensively 7
   • Consider aspirin for secondary prevention if ASCVD risk is high 7

3. Complete urgent stroke workup if not already done, as NAION requires evaluation for carotid stenosis, cardiac emboli sources, and hypercoagulable states 5

4. Monitor closely for visual changes:

   • Educate patients to report any new visual symptoms immediately 5
   • Ensure regular ophthalmologic follow-up
   • Document baseline visual acuity and visual fields 6

Key Considerations for Tirzepatide Specifically

Tirzepatide offers unique advantages in NAION patients with diabetes:

• Superior glycemic control compared to other agents, which may reduce microvascular complications 7
• Significant weight loss (9.8% at 15mg/92mg dose), addressing obesity as a NAION risk factor 7
• Cardiovascular benefits similar to GLP-1RAs 7
• May improve blood pressure and lipid profiles 7

Important cautions:

• Diabetic retinopathy complications were reported with semaglutide (injectable), though causality remains unclear and may relate to rapid glucose improvement rather than direct drug effect 7
• Gastrointestinal side effects (nausea, vomiting) require slow up-titration 7
• Not recommended if eGFR <45 mL/min/1.73 m² 7

Critical Pitfalls to Avoid

• Never withhold proven cardiovascular and metabolic therapies based on theoretical risks with very low-quality evidence 3, 1, 2
• Do not confuse lack of proven treatment for NAION with lack of need for aggressive vascular risk factor management 5
• Always rule out arteritic AION (giant cell arteritis) first, as this requires immediate high-dose corticosteroids and delayed treatment causes irreversible bilateral blindness 5
• Do not overlook non-diabetic causes of neuropathy in diabetic patients, as multiple etiologies may coexist 8

Practical Recommendation

Initiate or continue Mounjaro in NAION patients with type 2 diabetes who have:

• Established cardiovascular disease or high cardiovascular risk 7
• Inadequate glycemic control on current therapy 7
• Obesity requiring weight management 7
• No contraindications (personal/family history of medullary thyroid cancer, MEN2, severe renal impairment) 7

The substantial proven benefits of cardiovascular risk reduction, glycemic control, and weight loss outweigh the theoretical and unproven risk of NAION recurrence or progression. 7, 1, 2