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medRxiv PreprintsInternational3 November 2026

Target Trial Emulation of Metformin for Dementia Prevention in All of Us: Robustness to Cohort and Confounder Definitions

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Metformin use has been associated with a lower risk of incident dementia than other antidiabetics. We perform target trial emulation and causal competing risk analysis in the NIH All of Us (AoU) Research Program database, contrasting the effects of metformin and sulfonylurea initiation on dementia onset and death without dementia. AoU's social and behavioral health data allowed us to test robustness to excluding such confounders, and we further adjusted for calendar year effects and prior antidiabetic exposure, using both semiparametric Cox proportional hazards (PH) models and nonparametric mo
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