Cardiovascular effectiveness and safety of SGLT2 inhibitors vs DPP4 inhibitors by dementia status: a cohort study of older adults with diabetes
Authors' conclusion
While SGLT2i might provide cardiorenal protection among those with dementia, closer monitoring may be warranted due to greater susceptibility to diabetic ketoacidosis.
Study context
- Population
- Community-dwelling adults aged ≥66 years with diabetes initiating SGLT2i or DPP4i (2016–2022), Ontario, Canada; stratified by dementia status2,481 pairs with dementia
- Exposure
- SGLT2i vs DPP4i initiation, by dementia status
- Outcome
- Composite of:
- All-cause mortality or hospitalisation for ischaemic stroke
- MI
- HF
Methodological detailstarget trial emulation, propensity-score matched 1:1, stratified by dementia status, linkable administrative datasets
- Target trial emulation
- Propensity-score matched 1:1
- Stratified by dementia status
- Linkable administrative datasets
Main finding
As reported in the abstract
Composite effectiveness endpoint, by dementia status
IRD per 1000 person-years
−61.1
95% CI −78.2 to −43.9
Dementia; NNT: 20
IRD per 1000 person-years
−21.7
95% CI −23.7 to −19.7; homogeneity: p<0.001
No dementia; NNT: 43
Observational data: associations, not effects.
Further findings
| Outcome | IRD per 1000 person-years (95% CI) |
|---|---|
| All-cause mortality, dementiaNNT: 25 | −51.2 (−65.7 to −36.7) |
| Hospitalisation for HF, dementiaNNT: 99 | −16.4 (−24.6 to −8.2) |
Safety
| Outcome | IRD per 1000 person-years (95% CI) |
|---|---|
| Acute kidney injury, dementiaNNT: 76 | −39.7 (−55.0 to −24.4) |
| Genital infection, dementiaNNH: 64 | 9.7 (3.7–15.6) |
DKA, dementia vs no dementia
- Absolute increase in DKA with SGLT2i greater among those with dementia vs no dementia
- homogeneity: p=0.015
Original publication
Cardiovascular effectiveness and safety of SGLT2 inhibitors vs DPP4 inhibitors by dementia status: a cohort study of older adults with diabetes. Diabetologia. Published 8 November 2025. doi:10.
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