The role of antidiabetic drugs in the treatment of Alzheimer’s disease: systematic review

Abstract

Recent studies show that Alzheimer’s disease (AD) has many common links with conditions associated with insulin resistance, including neuroinflammation, impaired insulin signaling, oxidative stress, mitochondrial dysfunction and metabolic syndrome. The authors conducted an electronic search for publications in the PubMed/MEDLINE and Google Scholar databases using the keywords “amyloid beta”, “Alzheimer type-3-diabetes”, “intranasal insulin”, “metformin”, “type 2 diabetes mellitus”, “incretins” and “PPARy agonists». A systematic literature search was conducted among studies published between 2005 and 2022. The authors used the following inclusion criteria: 1) Subjects who received therapy for AD and/or DM2, if the expected result concerned the risk of cognitive decline or the development of dementia; 2) The age of the study participants is > 50 years; 3) The type of studies included in this review were randomized clinical trials, population-based observational studies or case-control studies, prospective cohort studies, as well as reviews and meta-analyses; 4) The included articles were written in English. In recent years, there has been considerable interest in identifying the mechanisms of action of antidiabetic drugs and their potential use in AD. Human studies involving patients with mild cognitive impairment and Alzheimer’s disease have shown that the administration of certain antidiabetic drugs, such as intranasal insulin, metformin, incretins and thiazolidinediones, can improve cognitive function and memory. The purpose of this study is to evaluate the effectiveness of antidiabetic drugs in the treatment of AD. According to the results of the study, metformin, intranasal insulin, thiazolidinediones and incretins showed a positive effect both in humans and in animal models. Recent studies show that thiazolidinediones can activate pathways in the brain that are regulated by IGF-1; however, rosiglitazone may pose a significant risk of side effects. The results of clinical studies on the use of metformin in AD are limited and contradictory.