Comparative Cardiovascular Outcomes of Tirzepatide and Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease. — VialBase Research
In 16,402 matched high-risk patients, tirzepatide was associated with a lower 1-year risk of major adverse cardiovascular events, death, limb events, and MI than GLP-1 receptor agonists.
- 16,402 patients with type 2 diabetes and atherosclerotic cardiovascular disease initiating tirzepatide or GLP-1 receptor agonists (Jan 2022-Mar 2025) were matched 1:1
- Tirzepatide was associated with a lower 1-year risk of major adverse cardiovascular events (HR 0.75, 95% CI 0.63-0.91) vs GLP-1 receptor agonists
- Reduced all-cause mortality (HR 0.69, 95% CI 0.53-0.90)
- Reduced major adverse limb events (HR 0.59, 95% CI 0.39-0.88) and acute myocardial infarction (HR 0.70, 95% CI 0.53-0.93)
- Results were robust across subgroups and sensitivity analyses
Summary
This retrospective, propensity score-matched cohort study used the TriNetX network to compare 1-year cardiovascular outcomes between tirzepatide and GLP-1 receptor agonists in patients with type 2 diabetes and established atherosclerotic cardiovascular disease. A total of 16,402 patients initiating either therapy between January 2022 and March 2025 were matched 1:1. Tirzepatide was associated with a significantly lower risk of major adverse cardiovascular events and several secondary cardiovascular outcomes over one year.
Key Findings
- 16,402 patients with type 2 diabetes and atherosclerotic cardiovascular disease were matched 1:1 (tirzepatide vs GLP-1 receptor agonists).
- Primary outcome, 1-year major adverse cardiovascular events: HR 0.75 (95% CI 0.63-0.91) favoring tirzepatide.
- All-cause mortality: HR 0.69 (95% CI 0.53-0.90).
- Major adverse limb events: HR 0.59 (95% CI 0.39-0.88).
- Acute myocardial infarction: HR 0.70 (95% CI 0.53-0.93).
- Results were robust across subgroups and sensitivity analyses.
Relevance to Tirzepatide
This active-comparator study addresses a clinically important question: whether tirzepatide’s dual GIP/GLP-1 mechanism confers cardiovascular advantages over GLP-1 receptor agonists alone in a high-risk secondary-prevention population. The consistent direction of effect across MACE, mortality, limb events, and myocardial infarction strengthens the cardiometabolic rationale for tirzepatide, while the retrospective design and absence of a specified individual GLP-1 comparator (e.g. Semaglutide) mean prospective trials are needed for confirmation. It complements outcome data on venous thromboembolism and positions tirzepatide favorably relative to the broader incretin class.
Citation
Wu JY, Lee KW, Kao CL, et al. Comparative Cardiovascular Outcomes of Tirzepatide and Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease. Journal of the American Heart Association. 2026. doi:10.1161/JAHA.125.047018.
See Also
- Parent compound: Tirzepatide
- Semaglutide
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