Deciphering the Roles of Metformin in Alzheimer’s Disease: A Snapshot

Abstract

Alzheimer’s disease (AD) is a prevalent neurodegenerative disease predominantly affecting millions of elderly people. To date, no effective therapy has been identified to reverse the progression of AD. Metformin, as a first-line medication for Type 2 Diabetes Mellitus (T2DM), exerts multiple beneficial effects on various neurodegenerative disorders, including AD. Evidence from clinical studies has demonstrated that metformin use contributes to a lower risk of developing AD and better cognitive performance, which might be modified by interactors such as diabetic status and APOE-ε4 status. Previous mechanistic studies have gradually unveiled the effects of metformin on AD pathology and pathophysiology, including neuronal loss, neural dysfunction, amyloid-β (Aβ) depositions, tau phosphorylation, chronic neuroinflammation, insulin resistance, impaired glucose metabolism and mitochondrial dysfunction. Current evidence remains ambiguous and even conflicting. Herein, we review the current state of knowledge concerning the mechanisms of metformin in AD pathology while summarizing current evidence from clinical studies.

Metformin: Is it a drug for all reasons and diseases?

“…As was indicated in a 2022 narrative review by Liao et al [397] of the potential role for metformin in offsetting the development of Alzheimer's disease the evidence of benefits remains ambiguous, despite data from preclinical studies providing potential mechanisms of action for metformin as a neuro-protective drug. Furthermore, the data from clinical studies are not universally positive thus raising concerns overextending the use of metformin to patients without T2D.…”

SIRT1 pathway in Parkinson’s disease: a faraway snapshot but so close

“…Taken together, NF-κB and NLRP3 inflammasome are activated in PD neuropathology and linked with the development of neuroinflammation (Paudel et al 2020 ). It has been shown that antagonistic crosstalk between SIRT1 and NF-κB is present to regulate energy metabolism and innate immunity (Liao et al 2021 ). NF-κB regulates immunity defense while SIRT1 controls inflammatory signaling pathways and cellular survival.…”

Effect of renin‐angiotensin system antihypertensive medication use on cognitive function in diabetes mellitus with obesity or overweight: An ancillary study to the Action for Health in Diabetes (Look AHEAD) trial

“…We cannot ignore the potential role of diabetes medication in AD pathology, especially metformin, which has been reported to decrease dementia risk by reducing vascular risk and to provide neuroprotection independently of glycaemic control 37 ; however, both AHM‐user groups reported a similar frequency of metformin use.…”