Heterogeneous treatment effects of sodium‐glucose cotransporter 2 inhibitors on risk of dementia in people with type 2 diabetes: A population‐based cohort study

INTRODUCTION Sodium‐glucose cotransporter 2 (SGLT2) inhibitors exhibit potential benefits in reducing dementia risk, yet the optimal beneficiary subgroups remain uncertain. METHODS Individuals with type 2 diabetes (T2D) initiating either SGLT2 inhibitor or sulfonylurea were identified from OneFlorida+ Clinical Research Network (2016–2022). A doubly robust learning was deployed to estimate risk difference (RD) and 95% confidence interval (CI) of all‐cause dementia. RESULTS Among 35,458 individuals with T2D, 1.8% in the SGLT2 inhibitor group and 4.7% in the sulfonylurea group developed all‐cause dementia over a 3.2‐year follow‐up, yielding a lower risk for SGLT2 inhibitors (RD, –2.5%; 95% CI, –3.0% to –2.1%). Hispanic ethnicity and chronic kidney disease were identified as the two important variables to define four subgroups in which RD ranged from –4.3% (–5.5 to –3.2) to –0.9% (–1.9 to 0.2). DISCUSSION Compared to sulfonylureas, SGLT2 inhibitors were associated with a reduced risk of all‐cause dementia, but the association varied among different subgroups. Highlights New users of sodium‐glucose cotransporter 2 (SGLT2) inhibitors were significantly associated with a lower risk of all‐cause dementia as compared to those of sulfonylureas. The association varied among different subgroups defined by Hispanic ethnicity and chronic kidney disease. A significantly lower risk of Alzheimer's disease and vascular dementia was observed among new users of SGLT2 inhibitors compared to those of sulfonylureas.