Metformin use associated with reduced risk of dementia in patients with diabetes: a systematic review and meta-analysis

Jared M. Campbell*, Matthew D. Stephenson, Barbora De Courten, Ian Chapman, Susan M. Bellman, Edoardo Aromataris

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

113 Citations (Scopus)
9 Downloads (Pure)


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.

Original languageEnglish
Pages (from-to)1225-1236
Number of pages12
JournalJournal of Alzheimer's Disease
Issue number4
Publication statusPublished - 25 Sep 2018

Bibliographical note

Copyright © 2018 IOS Press and the authors. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.


  • Alzheimer's disease
  • cognitive dysfunction
  • dementia
  • diabetes mellitus
  • meta-analysis
  • metformin
  • systematic review


Dive into the research topics of 'Metformin use associated with reduced risk of dementia in patients with diabetes: a systematic review and meta-analysis'. Together they form a unique fingerprint.

Cite this