Tirzepatide and Risk of Embolic Stroke or CRAO
Based on current evidence, tirzepatide has not been found to be associated with a higher risk of embolic stroke or central retinal artery occlusion (CRAO). In fact, available data suggest tirzepatide does not increase cardiovascular risk and may reduce stroke risk compared to control treatments.
Evidence from Cardiovascular Safety Studies
The most comprehensive cardiovascular safety data for tirzepatide comes from a pre-specified meta-analysis of seven randomized controlled trials including 4,887 tirzepatide-treated participants and 2,328 controls, which found no increased risk of major adverse cardiovascular events (MACE), with a hazard ratio of 0.80 (95% CI, 0.57-1.11) for the composite endpoint of cardiovascular death, myocardial infarction, stroke, and hospitalized unstable angina 1. This analysis specifically examined stroke as a component of MACE and found no safety signal.
The SURPASS-4 trial, which enrolled 1,995 participants with type 2 diabetes and high cardiovascular risk, demonstrated that tirzepatide was not associated with excess cardiovascular risk compared to insulin glargine, with adjudicated MACE-4 events showing a hazard ratio of 0.74 (95% CI, 0.51-1.08) 2.
Stroke events specifically were included in the adjudicated cardiovascular outcomes, and no increased risk was observed with tirzepatide treatment 2.
Comparison with GLP-1 Receptor Agonists
While tirzepatide's evidence for stroke is still accumulating, the broader class of GLP-1 receptor agonists (which tirzepatide partially mimics through its dual GIP/GLP-1 mechanism) has demonstrated stroke reduction rather than increased risk:
A 2024 systematic review for the American College of Physicians found that GLP-1 agonists reduce stroke with a relative risk of 0.86 (95% CI, 0.77-0.95) compared to usual care 3.
Evidence for tirzepatide specifically on stroke outcomes remains insufficient in this meta-analysis, but no safety signals have emerged 3.
Central Retinal Artery Occlusion Context
CRAO is fundamentally an embolic phenomenon sharing the same pathophysiology as cerebral ischemic stroke, with common risk factors including carotid stenosis, atrial fibrillation, and cardiovascular disease 3:
The incidence of CRAO is 1.9 per 100,000 person-years in the United States, rising to 10.1 per 100,000 in those over 80 years 3.
CRAO is most strongly associated with ipsilateral internal carotid artery stenosis (37-40% of cases have critical carotid disease) and emboli from cardiac sources 3.
Up to 27-76% of CRAO patients have concurrent silent cerebral infarctions on diffusion-weighted MRI, emphasizing the shared embolic pathophysiology 3.
Given that tirzepatide does not increase stroke risk and may reduce cardiovascular events, there is no mechanistic or clinical evidence to suggest it would increase CRAO risk, which shares the same embolic pathophysiology.
Ongoing Cardiovascular Outcomes Research
The SURMOUNT-MMO trial is currently enrolling approximately 15,000 participants to investigate tirzepatide's impact on a composite outcome including nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, heart failure events, and all-cause mortality in adults with obesity without diabetes 4.
Until these definitive cardiovascular outcome trial results are available, clinicians should recognize that existing evidence shows no increased risk of embolic events with tirzepatide 5, 1.
Clinical Implications
For patients requiring cardiovascular risk reduction, GLP-1 receptor agonists with established cardiovascular benefits (liraglutide, semaglutide) may be preferred until tirzepatide's cardiovascular outcome trial is completed 5. However, the absence of any safety signal for stroke or embolic events in completed tirzepatide trials provides reassurance that tirzepatide does not increase these risks.
Tirzepatide should be considered primarily for its proven benefits in glycemic control and substantial weight reduction (approximately 21% at 72 weeks with 15mg dose) 5, 6.
In the SUMMIT trial, tirzepatide demonstrated comprehensive cardiovascular benefits in patients with heart failure with preserved ejection fraction and obesity, reducing the combined risk of cardiovascular death or worsening heart failure 7.