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Cited by 176Folate and B Vitamins ResearchMetabolism, Diabetes, and CancerPorphyrin Metabolism and Disorders

Vitamin B12 Status in Metformin Treated Patients: Systematic Review

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Liu, Qilin, Li, Sheyu, Quan, Heng, Li, Jianwei·2014·PLoS ONE
DOI 10.1371/journal.pone.0100379PMC PMC4069007
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Abstract

OBJECTIVE: Randomized controlled trials and observational studies have yielded inconsistent results on the effects of metformin on vitamin B12 reduction. We therefore performed a systematic review to analyze the effects of metformin on vitamin B12 concentration. METHODS: PubMed, Medline, Embase, and the Cochrane central registry of controlled trials were searched to identify randomized controlled trials and observational studies exploring the association between metformin and vitamin B12 concentration in patients with type 2 diabetes mellitus or polycystic ovary syndrome. The main outcome measure was changes in serum vitamin B12 concentration after 6-208 weeks of treatment with metformin, as compared with placebo or other anti-hyperglycemic therapy. RESULTS: Six randomized controlled trials met the inclusion criteria. Serum vitamin B12 concentrations were significantly lower in patients treated with metformin than in those who received placebo or rosiglitazone (mean difference [MD], -53.93 pmol/L; 95% confidence interval [CI], -81.44 to -26.42 pmol/L, P = 0.0001). Subgroup analysis identified four trials in which patients received a lower dose of metformin (<2000 mg/d) and two in which they received a higher dose (≥2000 mg/d), with MDs in vitamin B12 concentration after metformin treatment of -37.99 pmol/L (95% CI, -57.44 to -18.54 pmol/L, P = 0.0001) and -78.62 pmol/L (95% CI, -106.37 to -50.86 pmol/L, P<0.00001), respectively. CONCLUSIONS: The reduction of vitamin B12 may be induced by metformin in a dose dependent manner.

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  • Recent literature suggests a possible dose-dependent effect of metformin on vitamin B12 absorption, though it is often not clinically significant.

    “Emerging literature including a recent systematic review is suggestive of a possible dose dependent effect of metformin on vitamin B12 absorption (Liu et al. , 2014), although this is often not clinically significant.”

    From Metformin and lifestyle modification in polycystic ovary syndrome: systematic review and meta-analysis (2015) · cites this paper as Liu et al. , 2014

    The Results report that vitamin B12 concentration fell more in the higher-dose than the lower-dose metformin group. The Discussion proposes malabsorption as a possible mechanism, but the review does not establish a dose-dependent effect on absorption itself. It describes the clinical significance of lower B12 concentrations as controversial, rather than establishing that the effect is often not clinically significant. (LLM, conf=0.85)

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References 44 · Cited by 176

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Authors
Liu, Q., Li, S., Quan, H., & Li, J.
Affiliations
West China Hospital of Sichuan University (CN)
Corresponding author
Li, Jianwei
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2014-06-24
Volume
9
Issue
6
Pages
e100379
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0100379
PMC
PMC4069007
OpenAlex
W1971438651
Cited by
176
References
44
Citations by year
2026: 6 · 2025: 11 · 2024: 14 · 2023: 22 · 2022: 17 · 2021: 14 · 2020: 22 · 2019: 18 · 2018: 15 · 2017: 17 · 2016: 13 · 2015: 6 · 2014: 1
FWCI
2.03
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • National Natural Science Foundation of China (30600293)
  • Sichuan University
  • West China Hospital, Sichuan University
Topics
  • Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
Keywords
metformin, vitamin B12, serum vitamin B12 concentration, type 2 diabetes, polycystic ovary syndrome, rosiglitazone, vitamin B12 deficiency
MeSH terms
Diabetes Mellitus, Type 2, Female, Humans, Hypoglycemic Agents, Metformin, Polycystic Ovary Syndrome, Vitamin B 12, Randomized Controlled Trials as Topic, Treatment Outcome

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