Tirzepatide Does Not Cause Myocardial Infarction
Tirzepatide does not cause myocardial infarction and is actually associated with reduced cardiovascular risk, including lower rates of MI, in patients with type 2 diabetes and established cardiovascular disease. 1
Evidence of Cardiovascular Safety and Benefit
Randomized Controlled Trial Data
The most recent and highest quality evidence comes from the 2025 SURPASS-CVOT trial, which directly assessed cardiovascular outcomes in 13,165 patients with type 2 diabetes and atherosclerotic cardiovascular disease. Tirzepatide demonstrated noninferiority to dulaglutide (a proven cardioprotective GLP-1 receptor agonist) with a hazard ratio of 0.92 (95.3% CI: 0.83-1.01) for the composite endpoint of cardiovascular death, myocardial infarction, or stroke. 1 This means tirzepatide did not increase MI risk and showed a trend toward benefit, though it did not reach statistical superiority over dulaglutide. 1
The earlier SURPASS-4 trial (2021) in 1,995 patients with type 2 diabetes and high cardiovascular risk showed that adjudicated MACE-4 events (cardiovascular death, MI, stroke, hospitalization for unstable angina) were not increased with tirzepatide compared to insulin glargine (HR: 0.74,95% CI: 0.51-1.08). 2 This demonstrates clear cardiovascular safety with a signal toward benefit. 2
Meta-Analysis Findings
A pre-specified cardiovascular meta-analysis of 7,215 participants across seven randomized controlled trials found that tirzepatide did not increase the risk of major cardiovascular events versus controls (HR for MACE-4: 0.80,95% CI: 0.57-1.11). 3 The hazard ratio for myocardial infarction specifically was 0.80 (95% CI: 0.51-1.25), indicating no increased risk and a numerical trend toward protection. 3
Real-World Evidence
The most compelling recent data comes from a 2025 observational study of 47,719 adults with type 2 diabetes, obesity, and pre-existing ischemic heart disease. After propensity score matching, tirzepatide was associated with a 41% lower risk of acute myocardial infarction compared to GLP-1 receptor agonists (HR: 0.59,95% CI: 0.38-0.91). 4 The composite outcome of MI, ischemic stroke, and all-cause mortality was also significantly reduced (HR: 0.60,95% CI: 0.43-0.84). 4
Important Clinical Context
Current Guideline Positioning
While tirzepatide demonstrates cardiovascular safety, it currently lacks the same level of proven cardiovascular benefit as semaglutide and liraglutide, which have robust MACE reduction data. 5 The American College of Physicians explicitly states that tirzepatide lacks adequate data for MACE outcomes compared to established GLP-1 agonists. 5
For patients requiring proven cardiovascular benefit as the primary therapeutic goal, semaglutide or liraglutide should be selected over tirzepatide until SURPASS-CVOT results are fully published and incorporated into guidelines. 5 However, the 2025 SURPASS-CVOT data now provides strong evidence of cardiovascular safety and likely benefit. 1
Mechanism of Cardioprotection
Tirzepatide's dual GIP/GLP-1 receptor agonism provides multiple cardioprotective mechanisms beyond glucose control, including anti-inflammatory effects, reduced platelet aggregation, improved endothelial function, and anti-atherosclerotic properties. 6 Recent preclinical data suggests tirzepatide enhances branched-chain amino acid catabolism, which reduces cardiomyocyte necrosis and inflammatory infiltration following MI. 7
Common Pitfalls to Avoid
Do not confuse cardiovascular safety with causation of MI. The evidence consistently shows tirzepatide does not cause MI and likely reduces MI risk. 2, 1, 3, 4
Do not assume all incretin-based therapies have identical cardiovascular profiles. Even within the GLP-1 class, only semaglutide and liraglutide have robust cardiovascular benefit data, while lixisenatide and exenatide do not. 5 Tirzepatide's dual mechanism makes it distinct. 8
Do not withhold tirzepatide due to MI concerns in patients with established cardiovascular disease. The SURPASS-4 and SURPASS-CVOT trials specifically enrolled high-risk cardiovascular patients and demonstrated safety. 2, 1
Do not overlook the gastrointestinal side effects (nausea 12-23%, diarrhea 13-22%) which are more common than with comparators but are typically mild-to-moderate and occur during dose escalation. 2 These should not be confused with cardiovascular risks.