Tirzepatide and the risk of atherosclerotic cardiovascular events: population based cohort study

doi:10.1136/bmj-2026-100011

Cardiometabolic & kidneyCohort study

Tirzepatide and the risk of atherosclerotic cardiovascular events: population based cohort study

BMJPublished 5 Aug 2026

Population based cohort study
propensity score overlap weighting
benchmarked against randomised trials
active comparator (placebo proxy)

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Authors' conclusion

In this cohort study using an approach benchmarked against randomised trials, initiating tirzepatide reduced the risk of MACE compared with a placebo proxy among people with type 2 diabetes and established atherosclerotic cardiovascular disease.

Study context

Population: Adults aged ≥40 years with T2DM and established atherosclerotic CVD, two national US claims databases, May 2022 to May 2025
Participants: 52,971 adults

Exposure: Tirzepatide vs sitagliptin, added to standard of care
Tirzepatiden = 35,353
Sitagliptinn = 17,618reference
Outcome: Major adverse cardiovascular events (MACE):
MI
Stroke
All cause mortality
Follow-up: One year

Main finding

As reported in the abstract

MACE

Tirzepatide2.9%weighted one year risk · 95% CI 2.5%–3.4%

Sitagliptin4.4%weighted one year risk · 95% CI 3.8%–4.9%

Tirzepatide vs SitagliptinRisk difference (95% CI)

NNT=70

−1.4%(−2.1% to −0.7%)

Tirzepatide vs SitagliptinHazard ratio (95% CI)

MACE

0.68(0.58–0.80)

Observational data: associations, not effects.

Further findings

Outcome	Lower risk with tirzepatide ←→ Higher risk with tirzepatide	HR (CI)
MI · NNT=130		0.67 (0.52–0.87)
Ischaemic stroke · no meaningful difference; NNT 2500		0.91 (0.64–1.28)
All cause mortality · NNT=122		0.55 (0.42–0.72)
Infection related mortality · NNT=200		0.40 (0.26–0.61)
	0.20.5125Hazard ratio (log scale)

Negative control outcomes (lumbar radiculopathy, abdominal hernia)

Negative control outcomes showed no association

Safety

Outcome	Lower risk with tirzepatide ←→ Higher risk with tirzepatide	HR (CI)
Infections requiring hospital admission · NNT=48		0.64 (0.55–0.75)
	0.512Hazard ratio (log scale)

Original publication

Tirzepatide and the risk of atherosclerotic cardiovascular events: population based cohort study. BMJ. Published 5 August 2026. doi:10.1136/bmj-2026-100011

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