Causal inference in medical records and complementary systems pharmacology for metformin drug repurposing towards dementia.

ABSTRACT: Metformin, a diabetes drug with anti-aging cellular responses, has complex actions that may alter dementia onset. Mixed results are emerging from prior observational studies. To address this complexity, we deploy a causal inference approach accounting for the competing risk of death in emulated clinical trials using two distinct electronic health record systems. In intention-to-treat analyses, metformin use associates with lower hazard of all-cause mortality and lower cause-specific hazard of dementia onset, after accounting for prolonged survival, relative to sulfonylureas. In parallel systems pharmacology studies, the expression of two AD-related proteins, APOE and SPP1, was suppressed by pharmacologic concentrations of metformin in differentiated human neural cells, relative to a sulfon

SUBMITTER: Charpignon ML 

PROVIDER: S-EPMC9741618 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature