Cardiometabolic & kidney

Cardiovascular outcomes of semaglutide and tirzepatide for patients with type 2 diabetes in clinical practice

Nat MedPublished Target trial emulation cohort studies

Main finding · MI, stroke or all-cause mortality (head-to-head)Result — go to the resultHazard ratio 1.06 95% CI 0.95–1.18

Authors' conclusion

These findings support a comparable cardiovascular benefit of tirzepatide and semaglutide in clinical practice

Study context

Population
Patients with elevated CV risk, including obesity and T2DM, in US insurance programs, 2018–2025
Exposure
Tirzepatide vs semaglutide
Outcome
Composite of:
  • MI
  • Stroke
  • All-cause mortality
Methodological detailsfive cohort studies, propensity-score matched, trial emulation (SUSTAIN-6, SURPASS-CVOT), head-to-head comparison
  • Five cohort studies
  • Propensity-score matched
  • Trial emulation (SUSTAIN-6, SURPASS-CVOT)
  • Head-to-head comparison

Main finding

MI, stroke or all-cause mortality (head-to-head)

Hazard ratio

1.06

95% CI 0.95–1.18

Tirzepatide vs Semaglutide
HR 1.06 (95% CI 0.95–1.18)

As reported in the abstract

Observational data: associations, not effects.

Further findings

OutcomeHR (95% CI)
MI or stroke, expanded populationSemaglutide vs Sitagliptin0.82 (0.74–0.91)
Composite including mortality, expanded populationTirzepatide vs Dulaglutide0.87 (0.75–1.01)

Trial emulation benchmarking

High agreement between reference trials and emulations for all individual endpoints except all-cause mortality in SUSTAIN-6

Original publication

Cardiovascular outcomes of semaglutide and tirzepatide for patients with type 2 diabetes in clinical practice. Nat Med. Published 9 November 2025. doi:10.1038/s41591-025-04102-x

Summarised from the published abstract; every number is checked against it

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