Does Mounjaro (tirzepatide) have the same risk of non‑arteritic anterior ischemic optic neuropathy (NAION) as semaglutide (Ozempic)?

Does Mounjaro (Tirzepatide) Have the Same Risk of NAION as Semaglutide?

Based on current evidence, tirzepatide appears to carry a similar—but not identical—risk profile for non-arteritic anterior ischemic optic neuropathy (NAION) compared to semaglutide, though the absolute risk remains very low and the evidence is still emerging.

Current Evidence on NAION Risk

Semaglutide Data

• A large retrospective matched cohort study of approximately 120,000 type 2 diabetes patients on semaglutide found no significant increase in NAION risk (RR = 0.7,95% CI: 0.523-0.937) compared to matched controls over 5 years, with a cumulative 5-year NAION risk of only 0.065%. 1
• Similarly, in patients with high BMI prescribed semaglutide, the 2-year risk of NAION was only 0.038%, with no significant increase compared to controls. 1
• However, individual case reports continue to document NAION occurring in patients taking semaglutide, suggesting the association remains controversial and requires ongoing surveillance. 2, 3

Tirzepatide Data

• Pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) from January 2022 to June 2025 identified 28 cases of ischemic optic neuropathy (ION) associated with tirzepatide as the primary suspect drug. 4
• Disproportionality analysis yielded significant safety signals (ROR: 2.599,95% CI: 1.778-3.799; PRR: 2.598,95% CI: 1.778-3.797), with Evans criteria supporting a "probable" drug-event association. 4
• The event is characterized as rare but serious, warranting cautious clinical consideration. 4

Key Mechanistic Considerations

Shared Risk Factors

• Both medications are GLP-1 receptor agonists (tirzepatide is a dual GIP/GLP-1 agonist), and NAION is already associated with the underlying conditions these drugs treat: type 2 diabetes, obesity, hypertension, and hyperlipidemia. 5
• The clinical development programs for semaglutide did not report any significant increase in NAION risk, though retrospective studies have suggested a possible link. 5

Diabetic Retinopathy Connection

• Semaglutide has been explicitly associated with diabetic retinopathy complications, predominantly in patients with prior history of proliferative retinopathy, likely due to rapid A1C reduction rather than direct drug toxicity. 6
• Patients should have a recent comprehensive eye examination before initiating semaglutide, particularly assessing for pre-existing diabetic retinopathy. 6
• The risks and benefits of semaglutide therapy should be considered carefully in patients with prior history of proliferative retinopathy. 6

Clinical Decision Algorithm

Pre-Treatment Assessment (Both Medications)

1. Obtain comprehensive ophthalmologic examination before initiating either tirzepatide or semaglutide if not performed within the last 12 months, specifically assessing for:

   • Pre-existing diabetic retinopathy (especially proliferative disease) 6
   • Optic nerve cup size ("disk at risk") 5
   • Optic nerve drusen 5

2. Screen for NAION risk factors:

   • Hypertension, hyperlipidemia, smoking, obstructive sleep apnea 5
   • Small optic nerve cup 5
   • Use of PDE-5 inhibitors, amiodarone, or cabergoline 5

Risk Stratification

• High-risk patients (proliferative diabetic retinopathy, small optic nerve cup, multiple vascular risk factors):

  • Consider alternative GLP-1 receptor agonists or SGLT2 inhibitors first 6
  • If GLP-1 RA is essential, implement slower dose titration to minimize rapid A1C reduction 6
  • Reduce total daily insulin dose by 20% when starting to slow glycemic improvement 6

• Standard-risk patients:

  • Proceed with standard titration protocols
  • Document informed consent discussion about optic nerve risks 6

Monitoring Protocol

• During treatment: Consider more frequent ophthalmologic monitoring (every 6 months rather than annually) in high-risk patients. 6
• Patient education: Instruct patients to report any sudden, painless vision loss immediately and discontinue medication. 2

Comparative Context

Tirzepatide vs. Semaglutide

• Tirzepatide shows stronger pharmacovigilance signals for ION/NAION in FAERS data (ROR: 2.599), though this may reflect reporting bias given increased public awareness. 4
• Semaglutide has larger real-world cohort data showing no significant risk increase, but individual case reports persist. 1, 2, 3
• Both medications share the mechanism of rapid glycemic improvement that may transiently worsen retinopathy. 6

Cardiovascular Benefits May Outweigh Risk

• Semaglutide provides a 26% reduction in major adverse cardiovascular events (HR 0.74,95% CI 0.58-0.95) in patients with established cardiovascular disease. 6
• The absolute risk of NAION remains extremely low (0.065% over 5 years for semaglutide), while cardiovascular benefits are substantial. 1, 6

Critical Caveats

• The association between GLP-1 RAs and NAION remains controversial, with conflicting results across studies. 3
• Clinicians should be aware of this possible association to analyze the risk-benefit ratio for each patient. 3
• Do not skip pre-treatment eye examination, even if the patient reports "no vision problems"—asymptomatic retinopathy is common. 6
• Avoid aggressive A1C reduction in patients with established retinopathy, as the mechanism appears related to rapidity of glucose lowering rather than the drug itself. 6

Bottom Line

While tirzepatide may carry a similar or slightly elevated signal for NAION compared to semaglutide based on pharmacovigilance data, the absolute risk remains very low for both medications. The decision should prioritize cardiovascular and metabolic benefits in appropriate patients, with careful pre-treatment ophthalmologic screening and informed consent discussion about this rare but serious potential risk. Patients with proliferative diabetic retinopathy or multiple NAION risk factors warrant particularly cautious consideration and closer monitoring.