Diabetes-Alzheimer's connection in older age: SGLT2 inhibitors as promising modulators of disease pathways

• Published in: Ageing research reviews Vol. 90; p. 102018
• Main Authors: Mancinetti, Francesca, Xenos, Dionysios, De Fano, Michelantonio, Mazzieri, Alessio, Porcellati, Francesca, Boccardi, Virginia, Mecocci, Patrizia
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01.09.2023
• Subjects: Aging; Dementia; Diabetes; Drugs; Metabolism; Drugs; Aging; Diabetes; Metabolism; Dementia; dementia; metabolism; aging; drugs; diabetes
• ISSN: 1568-1637; 1872-9649; 1872-9649
• DOI: 10.1016/j.arr.2023.102018

Late-onset Alzheimer's disease (LOAD) is the most frequent cause of dementia in older persons. Subjects affected by type 2 diabetes mellitus (T2DM) are at higher risk of vascular disease, cognitive decline, and dementia. LOAD has many characteristics shared with impaired insulin signaling pathways, and substantial evidence has demonstrated a pivotal role in dysregulated glucose metabolism in its pathogenesis. Recent studies have shown that some anti-diabetic drugs, other than regulating the metabolism of peripheral tissues, can also modulate the brain's metabolism, reduce inflammation, and have a direct neuroprotective effect. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a newer class with many pleiotropic effects that may have strong neuroprotective potential. After a summary of the principal "anti-diabetic" drugs acting as suitable candidates in treating LOAD, this narrative review explored the potential role of SGLT2i on cognition from pre-clinical to clinical studies. •Dementia incidence increases with age while Alzheimer's Disease (AD) is the most common type of dementia.•There is a close link among aging, type 2 diabetes mellitus (T2DM), and AD.•Approximately 80% of subjects with AD are affected by insulin resistance or have T2DM.•Insulin resistance and chronic hyperglycemia in T2DM may contribute to cognitive impairment in AD.•Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have shown potential neuroprotective effects.