Tirzepatide and the risk of atherosclerotic cardiovascular events: population based cohort study
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
Methodological detailspropensity score overlap weighting, benchmarked against randomised trials, active comparator (placebo proxy)
- Propensity score overlap weighting
- Benchmarked against randomised trials
- Active comparator (placebo proxy)
Main finding
As reported in the abstract
MACE
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 | HR (CI) | |
|---|---|---|
| MINNT=130 | 0.67 (0.52–0.87) | |
| Ischaemic strokeNo meaningful difference; NNT 2500 | 0.91 (0.64–1.28) | |
| All cause mortalityNNT=122 | 0.55 (0.42–0.72) | |
| Infection related mortalityNNT=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 | HR (CI) | |
|---|---|---|
| Infections requiring hospital admissionNNT=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.
Summarised from the published abstract; every number is checked against it