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Association between metformin and vitamin B12 deficiency in patients with Type 2 Diabetes: A systematic review and meta-analysis

Chapman, LE, Darling, AL and Brown, JE (2016) Association between metformin and vitamin B12 deficiency in patients with Type 2 Diabetes: A systematic review and meta-analysis Diabetes and Metabolism, 42 (5). pp. 316-327.


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Web Appendix A and B_ electronic searches and excluded studiesR1.pdf - Accepted version Manuscript

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Aim Metformin is the most widely used oral hypoglycaemic drug, but it may lower B12 status, which could have important clinical implications. We undertook a systematic review and meta-analysis of the relationship between metformin use and vitamin B12 deficiency in persons with type 2 diabetes. Methods Electronic database searches were undertaken (1st January 1957–1st July 2013) using the Cochrane library, Scopus, CINAHL, Grey literature databases, Pub Med Central, NICE Clinical Guidelines UK, and ongoing clinical trials. Included studies were of any study design, with data from patients with type 2 diabetes of any age or gender, taking any dose or duration of metformin. Planned primary outcomes were serum vitamin B12 levels, % prevalence or incidence of vitamin B12 deficiency and risk of vitamin B12 deficiency. Results Twenty-six papers were included in the review. Ten out of 17 observational studies showed statistically significantly lower levels of vitamin B12 in patients on metformin than not on metformin. Meta-analysis performed on four trials demonstrated a statistically significant overall mean B12 reducing effect of metformin of 57 pmol/L [WMD (fixed) = –0.57 (95% CI: –35 to –79 pmol/L)] after 6 weeks to 3 months of use. Conclusion The evidence from this review demonstrates an association between metformin usage and lower levels of vitamin B12 by 57 pmol/L, which leads to frank deficiency or borderline status in some patients with type 2 diabetes. This suggests that it is prudent to monitor B12 levels in these patients who are at increased risk of deficiency.

Item Type: Article
Subjects : Medical Science
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine > Department of Nutritional Sciences
Authors :
Chapman, LE
Darling, AL
Brown, JE
Date : 26 April 2016
DOI : 10.1016/j.diabet.2016.03.008
Copyright Disclaimer : © 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
Uncontrolled Keywords : Diabetes mellitus, Meta-analysis, Metabolic adverse effects, Oral hypoglycaemic agents, Primary care, Vitamin deficiency
Depositing User : Symplectic Elements
Date Deposited : 11 Jul 2016 15:31
Last Modified : 09 May 2017 08:12

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