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Metformin in the Prevention of Alzheimer’s Disease and Alzheimer’s Disease Related Dementias

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Abstract

Metformin is a safe and effective medication for Type 2 diabetes (T2D) that has been proposed to decrease the risk of aging related disorders including Alzheimer’s Disease (AD) and AD related disorders (ADRD). This review seeks to summarize findings from human and non-human studies examining the association of metformin with AD/ADRD related outcomes. Studies in animal models suggest that metformin could decrease the risk of AD/ADRD through multiple mechanisms including neuroprotective effects, decreasing neuroinflammation, and decreasing AD pathology. However, there are non-human studies that suggest that metformin could increase the risk of AD/ADRD. Observational human studies are also conflicting, but those with better study designs suggest that metformin use in persons with T2D is associated with a lower risk of dementia. However, these observational studies are limited by the use of administrative data to ascertain metformin use and/or cognitive outcomes. There are few clinical trials in persons without T2D that have small sample sizes and short durations but suggest that metformin could prevent AD/ADRD. There are ongoing studies including large clinical trials with long duration that are testing the effect of metformin on AD/ADRD outcomes in persons without T2D at risk for dementia.

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Acknowledgements

The authors wish to acknowledge the support of the National Institute on Aging from the National Institute of Health in the United States and the Alzheimer’s Disease Drug Discovery Foundation for some of the studies cited in this review. Dr. Luchsinger receives a stipend from Wolters Kluwer as an Editor in Chief of the journal Alzheimer’s Disease and Associated Disorders. He has been a consultant to Merck aKA in work related to metformin and currently receives extended release metformin and matching placebo from EMD Serono, subsidiary of Merck, for a clinical trial of metformin in amnestic mild cognitive impairment.

Funding

Funding: Dr. Luchsinger’s work in this review was supported by NIH grants R01AG062624, U19AG078558, and K24AG045334.

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  1. Department of Neurology, State University of New York Downstate Medical Center, new York, USA

    M. Tahmi

  2. Departments of Medicine and Epidemiology, Columbia University Irving Medical Center, 622 West 168th Street, PH9 Center room 210, New York, NY, 10032, USA

    José A. Luchsinger

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Correspondence to José A. Luchsinger.

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Conflict of interest: Dr. Luchsinger has been a consultant to Merck KGaA; the project funded by grant R01AG062624 receives metformin and matching placebo from EMD Serono, a business of Merck KGaA.

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Tahmi, M., Luchsinger, J.A. Metformin in the Prevention of Alzheimer’s Disease and Alzheimer’s Disease Related Dementias. J Prev Alzheimers Dis 10, 706–717 (2023). https://doi.org/10.14283/jpad.2023.113

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