Target trial emulations for tirzepatide, semaglutide and SGLT2-inhibitors for dementia in patients with type 2 diabetes: Real world evidence from a retrospective cohort study
Authors' conclusion
Tirzepatide is associated with a lower risk of dementia versus semaglutide and SGLT2-i in type 2 diabetes. Our findings are hypothesis generating, requiring confirmation in randomised controlled trials.
Study context
- Population
- Adults with T2D without dementia at baseline3 matched target trial emulations (TTEs)
- Exposure
- Tirzepatide vs semaglutide vs SGLT2i
- Outcome
- First diagnosis of dementia
- Follow-up
- 2 years
Methodological detailstarget trial emulations, three target trial emulations, propensity-score matched, real-world data, TriNetX global federated network
- Target trial emulations
- Three target trial emulations
- Propensity-score matched
- Real-world data, TriNetX global federated network
Main finding
As reported in the abstract
Incident dementia
Hazard ratio (95% CI)P value
Tirzepatidevs SemaglutideTTE3, n 12,246
0.69(0.48–0.99)
P = 0.04Tirzepatidevs SGLT2-iTTE1, n 14,462
0.66(0.47–0.93)
P = 0.02Observational data: associations, not effects.
Further findings
| Outcome | HR (95% CI) | P value | |
|---|---|---|---|
| All-cause mortality · 2 yearsTirzepatidevs Semaglutide | 0.72 (0.58–0.90) | P < 0.01 | |
| All-cause mortality · 2 yearsTirzepatidevs SGLT2-i | 0.29 (0.23–0.37) | P < 0.01 | |
| 0.20.5125Hazard ratio (log scale) |
MACE · 2 years
- Tirzepatide and semaglutide reduced MACE vs SGLT2-i
Matched cohort sizes
- TTE1 (tirzepatide vs SGLT2-i)
- 14,462
- TTE2 (semaglutide vs SGLT2-i)
- 57,959
- TTE3 (tirzepatide vs semaglutide)
- 12,246
Original publication
Target trial emulations for tirzepatide, semaglutide and SGLT2-inhibitors for dementia in patients with type 2 diabetes: Real world evidence from a retrospective cohort study. Diabetes Res Clin Pract. Published 14 January 2026. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →