Repositioning of Anti-Diabetic Drugs against Dementia: Insight from Molecular Perspectives to Clinical Trials

Insulin resistance as a hallmark of type 2 DM (T2DM) plays role in dementia by promoting pathological lesions or enhancing the vulnerability brain. Numerous studies related to insulin/insulin-like growth factor 1 (IGF-1) signaling are linked with various types dementia. Brain insulin is disturbances Aβ production and clearance, Tau hyperphosphorylation, microglial activation causing increased neuroinflammation, breakdown tight junctions blood–brain barrier (BBB). These mechanisms have been studied primarily Alzheimer’s disease (AD), but research on other forms like vascular (VaD), Lewy body (LBD), frontotemporal (FTD) has also explored overlapping mechanisms. Researchers currently trying repurpose anti-diabetic drugs treat dementia, which dominated sensitizers substrates. Although it seems promising feasible, none trials succeeded ameliorating cognitive decline late-onset We highlight possibility repositioning strategy for therapy reflecting current previous clinical trials. describe molecular perspectives through insulin/IGF-1 pathway.