Heterogeneous treatment effects of metformin on risk of dementia in patients with type 2 diabetes: A longitudinal observational study

Abstract

AbstractINTRODUCTIONLittle is known about the heterogeneous treatment effects of metformin on dementia risk in people with type 2 diabetes (T2D).METHODSParticipants (≥ 50 years) with T2D and normal cognition at baseline were identified from the National Alzheimer's Coordinating Center database (2005–2021). We applied a doubly robust learning approach to estimate risk differences (RD) with a 95% confidence interval (CI) for dementia risk between metformin use and no use in the overall population and subgroups identified through a decision tree model.RESULTSAmong 1393 participants, 104 developed dementia over a 4‐year median follow‐up. Metformin was significantly associated with a lower risk of dementia in the overall population (RD, –3.2%; 95% CI, –6.2% to –0.2%). We identified four subgroups with varied risks for dementia, defined by neuropsychiatric disorders, non‐steroidal anti‐inflammatory drugs, and antidepressant use.DISCUSSIONMetformin use was significantly associated with a lower risk of dementia in individuals with T2D, with significant variability among subgroups.