Effect of antidiabetic drugs in Alzheimer´s disease: a systematic review of preclinical and clinical studies

Abstract

The potential neuroprotective effects of antidiabetic treatments have been largely assessed in Alzheimer’s disease (AD) and AD-like dementia models, with or without metabolic disorders. In this Line, these effects Have also been addressed in wide population-based studies or in patients with mild cognitive impairment, AD, diabetes or combined pathologies. Most common treatments include glucagon-like peptide 1 receptor agonists; thiazolidinediones; biguanides; sulphonylureas; dipeptidyl peptidase-4 inhibitors, insulin, amylin and others. To assess their impact, we have conducted a systematic search in PubMed to Identify studies addressing the effect of Antidiabetic treatments on AD or AD-like dementia preclinical models And clinical studies, yielding 3560 research items. After screening titles And abstracts, 380 papers met eligibility criteria (original full-text articles, written in English, focused on AD or AD-like dementia, involving antidiabetic treatments, containing data on neuropathological AD markers and/or cognitive function, and conducted in vivo or ex vivo), And 25 additional papers were added through citations, resulting in a Total of 405 primary research articles published between 1996 And 2024. We have reviewed the effects of antidiabetic treatments on tau pathology, neuronal health, oxidative stress and neuroinflammation, vascular alterations, implicated signaling pathways and cognitive function in AD and AD-like dementia preclinical models and patients. Overall, antidiabetic medications represent a promising therapeutic strategy to tackle neurodegeneration and cognitive decline in AD preclinical models. Nevertheless, further research is needed to optimize their clinical effectiveness.