Background: SGLT2 inhibitors show promising associations with decreased dementia risk. However, it is unclear which population subgroups would benefit the most.

Methods: Using electronic health records data from the OneFlorida+ Clinical Research Network, we identified individuals with T2D (aged ≥ 50 years) who initiated SGLT2 inhibitors or sulfonylureas from Jan 1, 2016 - Jan 31, 2022. The study outcome was incident dementia. We applied a causal machine learning approach - doubly robust learning - to estimate the conditional average treatment effects (CATE) in the overall cohort and heterogeneous treatment effect subgroups using a summary decision tree model.

Results: Among 36,756 individuals with T2D, 3.2% in the SGLT2 inhibitor group and 6.4% in the sulfonylureas group developed dementia over a 3.4-year follow-up. In the overall cohort, SGLT2 inhibitors were associated with a lower risk of dementia (Risk Difference [RD], -10.3%; 95% confidence interval [CI], -12.0% to -8.6%) compared to sulfonylureas. We identified four subgroups with varying risks for dementia, determined by traumatic brain injury, ever-smoking, and epilepsy (Figure).

Conclusion: SGLT2 inhibitors were associated with a lower risk of dementia in people with T2D compared to sulfonylureas, with significant variability across subgroups.


H.Tang: None. C.Shaaban: None. Y.Wu: None. T.Magoc: None. W.T.Donahoo: None. S.T.Dekosky: Advisory Panel; Acumen Pharmaceuticals, Cognition Therapeutics, Other Relationship; Biogen, Prevail Pharmaceuticals, UpToDate, Up-To-Date. J.Bian: None. J.Guo: Consultant; Pfizer Inc., Research Support; PhRMA Foundation, NIH - National Institutes of Health.


National Institute of Diabetes and Digestive and Kidney Diseases (R01DK133465)

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