Sodium‐glucose cotransporter‐2 inhibitors and subtype‐specific dementia risk: A multinational and multiethnic cohort study
Authors' conclusion
This large-scale observational study suggests that SGLT2i use is associated with lower risks of multiple dementia subtypes and all-cause mortality in patients with T2DM.
Study context
- Population
- Adults with T2D initiating SGLT2i or DPP-4i, November 20, 2004–November 20, 2024; TriNetX electronic health records, 98 healthcare organizations worldwidematched cohort
- Participants
- 278,689 vs 278,689
- Exposure
- SGLT2i vs DPP-4i initiation
- SGLT2in = 278,689
- DPP4in = 278,689reference
- Outcome
- Overall dementia and dementia subtypes (vascular dementia (VaD), Alzheimer's disease (AD), other dementias)
Methodological detailsmultinational, propensity-score matched (1:1), TriNetX database
- Multinational
- Propensity-score matched (1:1)
- TriNetX database
Main finding
As reported in the abstract
Overall dementia
Each group vs DPP4iAdjusted hazard ratio (95% CI)
SGLT2i
0.77(0.75–0.79)
- SGLT2i
- aHR, vascular dementia 0.80
- SGLT2i
- aHR, Alzheimer's disease 0.82
- SGLT2i
- aHR, other dementias 0.68
Observational data: associations, not effects.
Secondary outcomes
| Outcome | SGLT2i | DPP4i | aHR (95% CI) | |
|---|---|---|---|---|
| All-cause mortality | 4.1% | 11.2% | 0.66 (0.65–0.68) | |
| 0.512Adjusted hazard ratio (log scale) |
Subgroups (age, sex, baseline glycaemic control, concurrent medication)
- Associations remained consistent across subgroups; findings robust in sensitivity analyses
Original publication
Sodium‐glucose cotransporter‐2 inhibitors and subtype‐specific dementia risk: A multinational and multiethnic cohort study. Diabetes Obes Metab. Published 10 April 2025. doi:10.
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