Comparative study of SGLT2 inhibitors and metformin: Evaluating first-line therapies for dementia prevention in type 2 diabetes
Main finding · Overall dementiaResult — go to the resultAdjusted hazard ratio 0.80 95 % CI 0.76–0.84Authors' conclusion
- SGLT2is significantly reduced dementia risk and mortality compared to metformin in T2D patients. These findings suggest SGLT2is may offer superior neuroprotective benefits, underscoring their potential as a first-line therapy for T2D. Further randomized trials are needed to confirm these results.
Study context
- Population
- Adults with T2D initiating SGLT2i or metformin as first-line therapymatched cohort
- Participants
- 74,975 vs 74,975
- Exposure
- SGLT2i vs metformin as first-line therapy
- SGLT2in = 74,975
- Metforminn = 74,975reference
- Outcome
- Overall dementia incidence, including vascular dementia, Alzheimer's disease and other subtypes
Methodological detailspropensity score-matched (1:1), TriNetX global federated network, over 98 healthcare organizations
- Propensity score-matched (1:1)
- TriNetX global federated network
- Over 98 healthcare organizations
Main finding
Overall dementia
Adjusted hazard ratio
0.80
95 % CI 0.76–0.84
By group
SGLT2ivs Metformin
aHR 0.80 (95 % CI 0.76–0.84)
As reported in the abstract
Observational data: associations, not effects.
Secondary outcomes
Vascular dementia
- Reductions were observed in vascular dementia
- aHR 0.87
Alzheimer's dementia
- Reductions were observed in Alzheimer's dementia
- aHR, 0.76
All-cause mortality
- Reductions were observed in all-cause mortality
- aHR, 0.92
Overall dementia by age
- Benefits pronounced in older adults, particularly those aged ≥80 years
Original publication
Comparative study of SGLT2 inhibitors and metformin: Evaluating first-line therapies for dementia prevention in type 2 diabetes. Diabetes Metab. Published 21 April 2025. doi:10.
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