Increased risk of cognitive impairment in patients with diabetes is associated with metformin

Document Type

Journal Article


American Diabetes Association


Faculty of Health, Engineering and Science


School of Medical Sciences / Centre of Excellence for Alzheimer's Disease Research and Care




This is an author-created, uncopyedited electronic version of an article accepted for publication in Diabetes. The American Diabetes Association (ADA), publisher of Diabetes, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. This article was originally published as: Moore, E., Mander, A., Ames, D., Kotowicz, M., Carne, R., Brodaty, H., Woodward, M., Boundy, K., Ellis, K., Bush, A., Faux, N., Martins, R. N., Szoeke, C., Rowe, C., & Watters, D. (2013). Increased risk of cognitive impairment in patients with diabetes is associated with metformin. Diabetes Care, 36(10), 2981-2987. The definitive publisher-authenticated version will be available in a future issue of Diabetes in print and online here


OBJECTIVE To investigate the associations of metformin, serum vitamin B12, calciumsupplements, and cognitive impairment in patients with diabetes. RESEARCH DESIGN AND METHODSdParticipants 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). RESULTSdParticipants 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]). CONCLUSIONSdMetformin use was associated with impaired cognitive performance. Vitamin B12 and calciumsupplementsmay 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.