Metformin and Risk of Alzheimer’s Disease Among Community-Dwelling People With Diabetes: A National Case-Control Study
Open accessAbstract
Context: Type 2 diabetes has been linked with an increased risk of Alzheimer’s disease (AD). Studies on the association between metformin use and AD have reported conflicting results. Objective: To investigate whether metformin use modifies the association between diabetes and incident, clinically verified AD. Design: Nested case-control study. Setting: All community-dwelling people in Finland. Participants: Cases were all community-dwelling Finns with AD diagnosed from 2005 to 2011 and with diabetes diagnosed ≥ 3 years before AD (n = 9862). Cases were matched with up to 2 control persons by age, sex, and diabetes duration (n = 19 550). Main outcome measure: Cumulative metformin exposure was determined from reimbursed dispensings over a 10- to 16-year period. Adjusted odds ratios (aORs) were calculated using conditional logistic regression to estimate associations, with adjustment for potential confounders. Results: A total of 7225 (73.3%) cases and 14528 (74.3%) controls received metformin at least once. Metformin use (ever use) was not associated with incident AD (aOR 0.99; 95% confidence interval [CI], 0.94–1.05). The adjusted odds of AD were lower among people dispensed metformin for ≥ 10 years (aOR 0.85; 95% CI, 0.76–0.95), those dispensed cumulative defined daily doses (DDDs) of < 1825–3650 (aOR 0.91; 95% CI, 0.84–0.98) and > 3650 DDDs (aOR 0.77; 95% CI, 0.67–0.88), and among persons dispensed an average of 2 g metformin daily (aOR 0.89; 95% CI, 0.82–0.96). Conclusion: In this large national sample we found no evidence that metformin use increases the risk of AD. Conversely, long-term and high-dose metformin use was associated with a lower risk of incident AD in older people with diabetes.
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Several clinical studies suggest long-term metformin therapy is associated with a lower risk of neurodegenerative diseases.
“several clinical studies suggest that long-term metformin therapy is associated with a lower risk of neurodegenerative diseases.524,525”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [525]
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Cites
IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045
Cho, N. H., Shaw, J. E., Karuranga, S., Huang, Y., da Rocha Fernandes, J. D., Ohlrogge, A. W., & Malanda, B. (2018) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2018.02.023 · Cited by 7,283 · see citing works
The projected effect of risk factor reduction on Alzheimer's disease prevalence
Barnes, D. E., & Yaffe, K. S. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70072-2 · Cited by 2,668 · see citing works
Nichols, E., Szoeke, C. E. I., Vollset, S. E., Abbasi, N., Abd-Allah, F., Abdela, J., Aichour, M. T. E., Akinyemi, R. O., Alahdab, F., Asgedom, S. W., et al. (2019) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30403-4 · Cited by 2,412 · see citing works
Risk of dementia in diabetes mellitus: a systematic review
Biessels, G. J., Staekenborg, S., Brunner, E., Brayne, C., & Scheltens, P. (2006) · The Lancet Neurology · doi:10.1016/s1474-4422(05)70284-2 · Cited by 2,187 · see citing works
Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota
MetaHIT consortium, Forslund, K., Hildebrand, F., Nielsen, T., Falony, G., Le Chatelier, E., Sunagawa, S., Prifti, E., Vieira-Silva, S., Gudmundsdottir, V., et al. (2015) · Nature · doi:10.1038/nature15766 · Cited by 2,116 · see citing works
2018 Alzheimer's disease facts and figures
Alzheimer's Association (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.02.001 · Cited by 1,912 · see citing works
The Gut Microbiota and Alzheimer’s Disease
Jiang, C., Li, G., Huang, P., Liu, Z., & Zhao, B. (2017) · Journal of Alzheimer's Disease · doi:10.3233/jad-161141 · Cited by 852 · see citing works
Diabetes mellitus and risk of dementia: A meta‐analysis of prospective observational studies
Gudala, K., Bansal, D., Schifano, F., & Bhansali, A. (2013) · Journal of Diabetes Investigation · doi:10.1111/jdi.12087 · Cited by 727 · see citing works
Molecular mechanism of action of metformin: old or new insights?
Rena, G., Pearson, E. R., & Sakamoto, K. (2013) · Diabetologia · doi:10.1007/s00125-013-2991-0 · Cited by 479 · see citing works
Imfeld, P., Bodmer, M., Jick, S. S., & Meier, C. R. (2012) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2012.03916.x · Cited by 389 · see citing works
Campbell, J. M., Stephenson, M. D., de Courten, B., Chapman, I., Bellman, S. M., & Aromataris, E. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180263 · Cited by 292 · see citing works
Diabetes Mellitus and the Risk of Alzheimer’s Disease: A Nationwide Population-Based Study
Huang, C., Chung, C., Leu, H., Lin, L., Chiu, C.-C., Hsu, C., Chiang, C.-H., Huang, P., Chen, T., Lin, S., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0087095 · Cited by 266 · see citing works
Use of Antidiabetic Drugs in the U.S., 2003–2012
Hampp, C., Borders‐Hemphill, V., Moeny, D. G., & Wysowski, D. K. (2014) · Diabetes Care · doi:10.2337/dc13-2289 · Cited by 214 · see citing works
From prescription drug purchases to drug use periods – a second generation method (PRE2DUP)
Tanskanen, A. J., Taipale, H. T., Koponen, M., Tolppanen, A., Hartikainen, S. A., Ahonen, R. S., & Tiihonen, J. (2015) · BMC Medical Informatics and Decision Making · doi:10.1186/s12911-015-0140-z · Cited by 200 · see citing works
Self-citationKuan, Y.-C., Huang, K.-W., Lin, C.-L., Hu, C.-J., & Kao, C.-H. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.06.002 · Cited by 168 · see citing works
Metformin vs sulfonylurea use and risk of dementia in US veterans aged ≥65 years with diabetes
Orkaby, A. R., Cho, K., Cormack, J. B., GAGNON, D. R., & Driver, J. A. (2017) · Neurology · doi:10.1212/wnl.0000000000004586 · Cited by 159 · see citing works
Changing use of antidiabetic drugs in the UK: trends in prescribing 2000–2017
Wilkinson, S., Douglas, I., Stirnadel-Farrant, H. A., Fogarty, D. G., Pokrajac, A., Smeeth, L. L., & Tomlinson, L. A. (2018) · BMJ Open · doi:10.1136/bmjopen-2018-022768 · Cited by 117 · see citing works
Benedict, C., & Grillo, C. A. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00215 · Cited by 96 · see citing works
Cohort profile: the Finnish Medication and Alzheimer's disease (MEDALZ) study
Tolppanen, A., Taipale, H. T., Koponen, M., Lavikainen, P., Tanskanen, A. J., Tiihonen, J., & Hartikainen, S. A. (2016) · BMJ Open · doi:10.1136/bmjopen-2016-012100 · Cited by 96 · see citing works
Self-citationMcMillan, J. M., Mele, B. S., Hogan, D. B., & Leung, A. A. (2018) · BMJ Open Diabetes Research & Care · doi:10.1136/bmjdrc-2018-000563 · Cited by 80 · see citing works
Taipale, H. T., Tanskanen, A. J., Koponen, M., Tolppanen, A., Tiihonen, J., & Hartikainen, S. A. (2016) · Clinical Epidemiology · doi:10.2147/clep.s116160 · Cited by 73 · see citing works
Self-citationTapiainen, V., Hartikainen, S. A., Taipale, H. T., Tiihonen, J., & Tolppanen, A. (2017) · European Psychiatry · doi:10.1016/j.eurpsy.2017.02.486 · Cited by 62 · see citing works
Self-citationMetformin and Sulfonylurea Use and Risk of Incident Dementia
Scherrer, J. F., Salas, J., Floyd, J. S., Farr, S. A., Morley, J. E., & Dublin, S. (2018) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2019.01.004 · Cited by 59 · see citing works
Metsärinne, K., Bröijersen, A., Kantola, I., Niskanen, L., Rissanen, A., Appelroth, T., Pöntynen, N., Poussa, T., Koivisto, V., & Virkamäki, A. (2015) · Primary Care Diabetes · doi:10.1016/j.pcd.2014.06.001 · Cited by 55 · see citing works
Unraveling Alzheimer’s: Making Sense of the Relationship between Diabetes and Alzheimer’s Disease
Schilling, M. A. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-150980 · Cited by 53 · see citing works
Impact of Insulin Sensitizers on the Incidence of Dementia: A Meta-Analysis
Ye, F., Luo, Y.-J., Xiao, J. F., Yu, N., & Yi, G. (2016) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000445941 · Cited by 47 · see citing works
Scherrer, J. F., Morley, J. E., Salas, J., Floyd, J. S., Farr, S. A., & Dublin, S. (2019) · The Annals of Family Medicine · doi:10.1370/afm.2415 · Cited by 38 · see citing works
Type 2 diabetes and treatment intensification in primary care in Finland
NISKANEN, L. K., Hahl, J., Haukka, J. K., Leppä, E., Miettinen, T. A., Mushnikov, V., Sipilä, R., Tamminen, N., Vattulainen, P., & Korhonen, P. (2018) · Acta Diabetologica · doi:10.1007/s00592-018-1199-7 · Cited by 16 · see citing works
Manski-Nankervis, J.-A. E., Thuraisingam, S., Sluggett, J. K., Lau, P. M.-Y., Blackberry, I., Ilomäki, J., Furler, J., & Bell, J. S. (2018) · Primary care diabetes · doi:10.1016/j.pcd.2018.09.001 · Cited by 15 · see citing works
Self-citationManski-Nankervis, J.-A. E., Thuraisingam, S., Sluggett, J. K., Kilov, G., Furler, J., O'Neal, D. N., & Jenkins, A. J. (2019) · BMC Family Practice · doi:10.1186/s12875-019-0915-x · Cited by 13 · see citing works
Self-citationSluggett, J. K., Koponen, M., Bell, J. S., et al. (2019) · Figshare · doi:10.26180/5dacf3217f8bd
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Santiago, J. A., & Potashkin, J. A. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.631770 · Cited by 259 · see citing works
Antidiabetic agents as a novel treatment for Alzheimer’s and Parkinson’s disease
Nowell, J., Blunt, E., Gupta, D., & Edison, P. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101979 · Cited by 179 · see citing works
Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances
Jiang, Q., Liu, J., Huang, S., Wang, X.-Y., Chen, X., Liu, G.-H., Ye, K., Song, W., Masters, C. L., Wang, J., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02145-7 · Cited by 165 · see citing works
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Liao, W., Xu, J., Li, B., Ruan, Y., Li, T., & Liu, J. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.728315 · Cited by 84 · see citing works
Tian, S., Jiang, J., Wang, J., Zhang, Z., Miao, Y., Ji, X., & Bi, Y. (2023) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3673 · Cited by 79 · see citing works
Stojakovic, A., Trushin, S., Sheu, A., Khalili, L., Chang, S.-Y., Li, X., Christensen, T., Salisbury, J. L., Geroux, R. E., Gateno, B., et al. (2021) · Communications Biology · doi:10.1038/s42003-020-01584-y · Cited by 72 · see citing works
Querfurth, H., Marshall, J., Parang, K., Rioult-Pedotti, M. S., Tiwari, R., Kwon, B., Reisinger, S., & Lee, H.-K. (2022) · PLOS ONE · doi:10.1371/journal.pone.0261696 · Cited by 9 · see citing works
- Authors
- Sluggett, J. K., Koponen, M., Bell, J. S., Taipale, H., Tanskanen, A., Tiihonen, J., Uusitupa, M., Tolppanen, A.-M., & Hartikainen, S.
- Affiliations
- Hornsby Ku-ring-gai Hospital (AU)
- University of Eastern Finland (FI)
- Corresponding author
- Sluggett, Janet K
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2019-11-28
- Volume
- 105
- Issue
- 4
- Pages
- e963-e972
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2990112732
- Cited by
- 95
- References
- 31
- Citations by year
- 2026: 3 · 2025: 18 · 2024: 16 · 2023: 17 · 2022: 19 · 2021: 11 · 2020: 10
- FWCI
- 7.95
- Type
- journal article
- Language
- en
- Open access
- green
- erepo.uef.fi
- Licence
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- UEF eRepo (University of Eastern Finland) (submittedVersion, other-oa)
- UniSA Research Outputs Repository (University of South Australia) (submittedVersion)
- Funders
- Eli Lilly and Company
- H. Lundbeck A/S
- National Health and Medical Research Council
- Cilag
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- metformin, Alzheimer's disease, type 2 diabetes, dementia risk, defined daily doses, community-dwelling older adults, drug exposure
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Alzheimer Disease, Blood Glucose, Diabetes Mellitus, Type 2, Female, Finland, Follow-Up Studies, Humans, Hypoglycemic Agents, Male, Metformin, Prognosis, Registries, Risk Factors, Biomarkers, Case-Control Studies, Independent Living
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