Increased Risk of Cognitive Impairment in Patients With Diabetes Is Associated With Metformin

  1. the AIBL Investigators*
  1. 1The University of Melbourne, Department of Psychiatry, Parkville, Victoria, Australia
  2. 2Barwon Health, Geelong, Victoria, Australia
  3. 3National Ageing Research Institute, Parkville, Victoria, Australia
  4. 4Deakin University School of Medicine, Waurn Ponds, Victoria, Australia
  5. 5North West Academic Centre, The University of Melbourne, Sunshine, Victoria, Australia
  6. 6Centre for Healthy Brain Ageing, University of New South Wales, School of Psychiatry, Sydney, Australia
  7. 7Aged Care Psychiatry, Prince of Wales Hospital, Randwick, New South Wales, Australia
  8. 8Austin Health, Heidelberg Repatriation Hospital, Heidelberg, Victoria, Australia
  9. 9The Queen Elizabeth Hospital, Woodville South, South Australia, Australia
  10. 10Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia
  11. 11Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia
  12. 12Centre of Excellence for Alzheimer’s Disease Research & Care, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia
  13. 13Sir James McCusker Alzheimer’s Disease Research Unit (Hollywood Private Hospital), Neurosciences Unit, Health Department of Western Australia, Perth, Western Australia, Australia
  14. 14Preventative Health Flagship, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Parkville, Victoria, Australia
  15. 15Austin PET Centre, Austin Hospital, Heidelberg, Victoria, Australia
  1. Corresponding author: Eileen M. Moore, eileen.moore{at} or dr.eileenmoore{at}


OBJECTIVE To investigate the associations of metformin, serum vitamin B12, calcium supplements, and cognitive impairment in patients with diabetes.

RESEARCH DESIGN AND METHODS Participants were recruited from the Primary Research in Memory (PRIME) clinics study, the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, and the Barwon region of southeastern Australia. Patients with Alzheimer disease (AD) (n = 480) or mild cognitive impairment (n = 187) and those who were cognitively intact (n = 687) were included; patients with stroke or with neurodegenerative diseases other than AD were excluded. Subgroup analyses were performed for participants who had either type 2 diabetes (n = 104) or impaired glucose tolerance (n = 22).

RESULTS Participants with diabetes (n = 126) had worse cognitive performance than participants who did not have diabetes (n = 1,228; adjusted odds ratio 1.51 [95% CI 1.03–2.21]). Among participants with diabetes, worse cognitive performance was associated with metformin use (2.23 [1.05–4.75]). After adjusting for age, sex, level of education, history of depression, serum vitamin B12, and metformin use, participants with diabetes who were taking calcium supplements had better cognitive performance (0.41 [0.19–0.92]).

CONCLUSIONS Metformin use was associated with impaired cognitive performance. Vitamin B12 and calcium supplements may alleviate metformin-induced vitamin B12 deficiency and were associated with better cognitive outcomes. Prospective trials are warranted to assess the beneficial effects of vitamin B12 and calcium use on cognition in older people with diabetes who are taking metformin.


  • Received January 27, 2013.
  • Accepted April 29, 2013.

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This Article

  1. Diabetes Care
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