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Risk Factors of Vitamin B12 Deficiency in Patients Receiving Metformin
Abstract
BACKGROUND: Identification of risk factors for metformin-related vitamin B(12) deficiency has major potential implications regarding the management of diabetes mellitus. METHODS: We conducted a nested case-control study from a database in which the source population consisted of subjects who had levels of both serum vitamin B(12) and hemoglobin A(1c) checked in a central laboratory. We identified 155 cases of diabetes mellitus and vitamin B(12) deficiency secondary to metformin treatment. Another 310 controls were selected from the cohort who did not have vitamin B(12) deficiency while taking metformin. RESULTS: A total of 155 patients with metformin-related vitamin B(12) deficiency (mean +/- SD serum vitamin B(12) concentration, 148.6 +/- 40.4 pg/mL [110 +/- 30 pmol/L]) were compared with 310 matched controls (466.1 +/- 330.4 pg/mL [344 +/- 244 pmol/L]). After adjusting for confounders, we found clinically important and statistically significant association of vitamin B(12) deficiency with dose and duration of metformin use. Each 1-g/d metformin dose increment conferred an odds ratio of 2.88 (95% confidence interval, 2.15-3.87) for developing vitamin B(12) deficiency (P<.001). Among those using metformin for 3 years or more, the adjusted odds ratio was 2.39 (95% confidence interval, 1.46-3.91) (P = .001) compared with those receiving metformin for less than 3 years. After exclusion of 113 subjects with borderline vitamin B(12) concentration, dose of metformin remained the strongest independent predictor of vitamin B(12) deficiency. CONCLUSIONS: Our results indicate an increased risk of vitamin B(12) deficiency associated with current dose and duration of metformin use despite adjustment for many potential confounders. The risk factors identified have implications for planning screening or prevention strategies in metformin-treated patients.
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“Vitamin B12 deficiency has been related with dose and duration of metformin use and occurs more frequently among patients that use it for more than 3 years and in higher doses [169].”
From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [169]
Citations
Cites
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Unmasking Pernicious Anemia: A Reversible Cause of Pancytopenia Due to Severe Vitamin B12 Deficiency
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Prevalence of Vitamin B12 Deficiency Among Type 2 Diabetes Patients on Metformin Therapy
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Geriatrische Aspekte bei Diabetes mellitus (Update 2026)
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The effects of metformin on metabolism and cardiovascular disease in type 2 diabetes
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Metadata
- Authors
- Ting, R. Z.-W.
- Affiliations
- Chinese University of Hong Kong (HK)
- Corresponding author
- Ting, Rose Zhao-Wei
- Venue
- Archives of Internal Medicine
- Publisher
- American Medical Association (AMA)
- Published
- 2006-10-09
- Volume
- 166
- Issue
- 18
- Pages
- 1975
- ISSN
- 0003-9926 (ISSN-L)
- OpenAlex
- W2146883482
- Cited by
- 333
- References
- 19
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 13 · 2023: 24 · 2022: 18 · 2021: 24 · 2020: 20 · 2019: 17 · 2018: 19 · 2017: 16 · 2016: 27 · 2015: 14 · 2014: 15 · 2013: 14 · 2012: 15
- FWCI
- 8.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Folate and B Vitamins Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
- Health Sciences › Medicine › Hematology › Hematological disorders and diagnostics
- Keywords
- vitamin B12 deficiency, metformin, metformin dose, diabetes mellitus, risk factors, drug-induced vitamin deficiency, screening
- MeSH terms
- Age Factors, Aged, Diabetes Mellitus, Dose-Response Relationship, Drug, Female, Hong Kong, Humans, Hypoglycemic Agents, Male, Metformin, Risk Factors, Vitamin B 12 Deficiency, Odds Ratio, Case-Control Studies, Databases as Topic
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