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Tirzepatide’s cardiovascular effects in clinical practice
Investigators compared cardiovascular outcomes with tirzepatide and a placebo proxy in patients with type 2 diabetes and established atherosclerotic cardiovascular disease.
To compare the 1-year risk of major adverse cardiovascular events (MACE) between tirzepatide and sitagliptin in patients with type 2 diabetes and established atherosclerotic cardiovascular disease.
Approach:
Study Design: A population-based cohort study analyzing de-identified administrative claims data from Optum Clinformatics and Merative MarketScan from May 2022 to May 2025.
Participants: 52,971 patients aged 40 years or older who initiated tirzepatide (n = 35,353) or sitagliptin (n = 17,618).
Eligibility Criteria: Patients had a documented previous myocardial infarction, ischemic stroke, or coronary, carotid, or peripheral arterial disease.
Outcome Measures: Primary outcome was MACE, defined as myocardial infarction, stroke, or all-cause mortality, with follow-up until MACE occurrence or 1 year.
Analysis Method: Propensity scores were estimated and overlap weighting was applied to balance baseline characteristics between treatment groups.
Key Findings:
At 1 year, weighted MACE risk was about 3% with tirzepatide vs. 4% with sitagliptin.
The risk of myocardial infarction or stroke was approximately 2% with tirzepatide and 3% with sitagliptin.
Tirzepatide was associated with lower risks of myocardial infarction and all-cause mortality compared to sitagliptin.
Fewer infection-related hospital admissions were noted with tirzepatide compared to sitagliptin.
Limitations:
Relatively short follow-up with mean on-treatment follow-up of 182 days.
Reliance on sitagliptin as a proxy for placebo.
Possible residual confounding and treatment or outcome misclassification in claims data.
Findings may not generalize to uninsured patients or non-US health care systems.
Conclusion:
The study found that tirzepatide was associated with a lower risk of MACE compared to sitagliptin in the studied population.
Investigators found that adding pregnancy-related and female-specific factors modestly improved postpartum cardiovascular risk prediction compared with traditional risk factors alone.
