Does Metformin Blunt Diabetes Link to Brain Aging?

Miriam E. Tucker, for Medscape

April 11, 2022

Researchers published the study covered in this summary on as a preprint that has not yet been peer reviewed.

Key Takeaways

  • Type 2 diabetes appears to markedly accelerate normal brain aging.

  • Metformin use does not appear to prevent neurocognitive decline.

Why This Matters

  • Although preliminary evidence links type 2 diabetes to neurologic and cognitive decline, patients don't typically undergo comprehensive neurocognitive evaluation as part of clinical care.

  • It is currently unknown whether neurocognitive effects represent a type 2 diabetes-specific neurodegenerative pathway or exacerbation of typical brain aging.

  • Few studies have addressed the impact of type 2 diabetes chronicity or treatment on neurocognitive decline.

Study Design

  • Neurocognitive effects independently associated with type 2 diabetes and age were examined in 20,314 individuals from the UK Biobank.

  • A separate meta-analysis evaluated 34 published cognitive studies (N = 22,231) and 60 neuroimaging studies, 30 of type 2 diabetes (N = 866) and 30 of aging (N = 1088). 

Key Results

  • In the UK Biobank, cognitive deficits beyond age-related effects were seen among those with type 2 diabetes, particularly an additional 13.1% decreased performance in executive function (P = .001) and a 6.7% greater decline in processing speed (P = .0002).

  • The meta-analysis confirmed further declines with type 2 diabetes in executive function (P = .009), processing speed (P ≤ .001), and numeric memory (approximately 2-3 seconds, P = .05), as well as abstract reasoning (P ≤ .001), verbal memory (P = .001), delayed (approximately 20 minute) verbal memory (P = .005), verbal fluency (P ≤ .001), visuospatial reasoning (P ≤ .001), and working memory (P = .002).

  • Compared to age-matched controls, those with type 2 diabetes had further decreases in gray matter including cortical and subcortical regions.

  • Structural and functional changes associated with type 2 diabetes overlapped with those associated with age but appeared earlier.

  • Neurodegeneration severity correlated with diabetes duration.

  • No differences in cognition or brain atrophy between those with type 2 diabetes who were or were not taking metformin was seen, after matching for disease duration and body mass index.


  • Use of a lifespan dataset permitted tracking how variables change with age, but not for the same individuals.

  • No information on A1c measures or other diabetes-related characteristics.


  • Study was funded by the W.M. Keck Foundation, the White House Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative, and the Baszucki Brain Research Fund.

  • One author reports serving on data monitoring committees for Novo Nordisk.

  • None of the authors received funding or in-kind support from pharmaceutical and/or other companies to write the manuscript.

This is a summary of a preprint research study "Type 2 diabetes mellitus accelerates brain aging and cognitive decline: complementary findings from UK Biobank and meta-analyses,” written by Botond Antal, Stony Brook University, New York, and Massachusetts General Hospital and Harvard Medical School, Charlestown, on medRxiv provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on


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