Comparative effectiveness of tirzepatide versus GLP-1 receptor agonists on cardiovascular–kidney–metabolic stage progression: a real-world cohort study
Main finding · Progression to CKM stage 3-4Result — go to the resultHazard ratio 0.88 95% CI 0.86–0.91Authors' conclusion
In this large real-world cohort of patients with early-stage CKM syndrome, initiation of tirzepatide was associated with a lower risk of progression from CKM stages 1-2 to stages 3-4 compared with other GLP-1 RAs, along with consistent reductions in multiple cardiovascular outcomes. These findings suggest that therapeutic choices made earlier along the CKM continuum may be associated with early differences in disease trajectories, although longer-term studies are needed to determine their sustained clinical impact.
Study context
- Population
- Adults with cardiovascular-kidney-metabolic (CKM) stage 1 or 2, TriNetX US Collaborative Network (January 2022-September 2025)matched cohort
- Participants
- 448,591 vs 448,591
- Exposure
- Tirzepatide vs other GLP-1 RAs
- Tirzepatiden = 448,591
- GLP-1 RAsn = 448,591reference
- Outcome
- Progression to CKM stage 3 or 4 (incident HF, coronary artery disease, ischemic stroke, AF, peripheral artery disease, or very high-risk CKD)
- Follow-up
- one-year follow-up
Methodological detailsnew-user design, 1:1 propensity score matching, TriNetX US Collaborative Network
- New-user design
- 1:1 propensity score matching
- TriNetX US Collaborative Network
Main finding
Progression to CKM stage 3-4
Hazard ratio
0.88
95% CI 0.86–0.91
P < 0.001
By group
As reported in the abstract
Observational data: associations, not effects.
Secondary outcomes
| Outcome | HR (95% CI) | |
|---|---|---|
| MACE | 0.85 (0.80–0.89) | |
| 0.512Hazard ratio (log scale) |
Coronary artery disease, peripheral artery disease, ischemic stroke, HF, very high-risk CKD, all-cause mortality
- Lower risks with tirzepatide
AF
- No significant difference
Prespecified subgroups (age, sex, baseline CKM stage, obesity status, statin use)
- Associations consistent across subgroups
Original publication
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