Metformin Use Associated With Reduced Risk of Dementia in Patients With Diabetes: A Systematic Review and Meta-Analysis
Open accessAbstract
BACKGROUND: Metformin, a first line antihyperglycemic medication, is an AMPK activator and has been hypothesized to act as a geroprotective agent. Studies on its association with various classifications of age-related cognitive decline have shown mixed results with positive and negative findings. OBJECTIVE: To synthesize the best available evidence on the association of metformin-use with risk, progression, and severity of dementia. METHOD: Eligible research investigated the effect of metformin on dementia, Alzheimer's disease, or any measure of cognitive impairment compared to any control group who were not receiving metformin. The initial search resulted in 862 citations from which 14 studies (seven cohort, four cross-sectional, two RCTs, and one case control) were included. RESULTS: Meta-analysis of three studies showed that cognitive impairment was significantly less prevalent in diabetic metformin (Odds ratio = 0.55, 95% CI 0.38 to 0.78), while six studies showed that dementia incidence was also significantly reduced (Hazard ratio = 0.76, 95% CI 0.39 to 0.88). Mini-Mental State Examination scores were not significantly affected by metformin-use, although both RCTs showed that metformin had a neuroprotective effect compared to placebo. Some studies found negative or neutral effects for metformin use by people with diabetes; the potential mechanism of metformin-induced vitamin B12 deficiency is discussed. CONCLUSIONS: Metformin should continue to be used as a first line therapy for diabetes in patients at risk of developing dementia or Alzheimer's disease. The use of metformin by individuals without diabetes for the prevention of dementia is not supported by the available evidence.
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Diabetes-associated hyperglycemia, hyperinsulinemia, elevated oxidative stress, vascular disease, and inflammation are all linked to cognitive decline.
“Diabetes-associated hyperglycemia, hyperinsulinemia, elevated oxidative stress, vascular disease, and inflammation are all linked to cognitive decline and, as reflected by a meta-analysis, it was concluded that metformin reduces cognitive decline and dementia in T2DM subjects (255).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [255]
A meta-analysis concluded that metformin reduces cognitive decline and dementia in T2DM subjects.
“Diabetes-associated hyperglycemia, hyperinsulinemia, elevated oxidative stress, vascular disease, and inflammation are all linked to cognitive decline and, as reflected by a meta-analysis, it was concluded that metformin reduces cognitive decline and dementia in T2DM subjects (255).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [255]
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- Authors
- Campbell, J. M., Stephenson, M. D., de Courten, B., Chapman, I., Bellman, S. M., & Aromataris, E.
- Affiliations
- The University of Adelaide (AU)
- Monash Centre for Health, Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
- National Health and Medical Research Council (AU)
- Corresponding author
- Campbell, Jared M.
- Venue
- Journal of Alzheimer s Disease
- Publisher
- SAGE Publications
- Published
- 2018-08-22
- Volume
- 65
- Issue
- 4
- Pages
- 1225-1236
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC6218120
- OpenAlex
- W2888308652
- Cited by
- 292
- References
- 56
- Citations by year
- 2026: 32 · 2025: 38 · 2024: 48 · 2023: 41 · 2022: 50 · 2021: 30 · 2020: 33 · 2019: 18 · 2018: 1
- FWCI
- 3.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Alzheimer s Disease (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Monash University Research Portal (Monash University) (submittedVersion, other-oa)
- RMIT Research Repository (RMIT University Library) (submittedVersion, other-oa)
- Figshare (submittedVersion, cc-by-nc)
- Funders
- Judith Jane Mason and Harold Stannett Williams Memorial Foundation
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- metformin, dementia
- MeSH terms
- Dementia, Diabetes Mellitus, Humans, Hypoglycemic Agents, Metformin, Disease Progression, Cognitive Dysfunction
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