Abstract

AimsTo compare the prevalence of vitamin B12 deficiency and peripheral neuropathy between two groups of type 2 diabetes mellitus (T2DM) patients treated with or without metformin, and to determine factors associated with vitamin B12 deficiency therapy and dietary intake of vitamin B12.MethodsIn this retrospective study, we recruited 412 individuals with T2DM: 319 taking metformin, and 93 non-metformin users. Demographics, dietary assessment for vitamin B12 intakes, and medical history were collected. Participants were assessed for peripheral neuropathy. Blood specimens were collected and checked for serum vitamin B12 levels. The differences between the two groups were analyzed using an independent t-test for continuous data, and the Chi-squared or Fisher's exact test was used for categorical data. The relationship of vitamin B12 deficiency with demographics and clinical characteristics was modeled using logistic regression.ResultsThe prevalence of B12 deficiency was 7.8% overall, but 9.4% and 2.2% in metformin users and non-metformin users, respectively. The odds ratio for serum vitamin B12 deficiency in metformin users was 4.72 (95% CI, 1.11–20.15, P = 0.036). There were no significant differences in a test of peripheral neuropathy between the metformin users and non-metformin users (P > 0.05). Low levels of vitamin B12 occurred when metformin was taken at a dose of more than 2,000 mg/day (AOR, 21.67; 95% CI, 2.87–163.47) or for more than 4 years (AOR, 6.35; 95% CI, 1.47–24.47).ConclusionIndividuals with T2DM treated with metformin, particularly those who use metformin at large dosages (> 2,000 mg/day) and for a longer duration (> 4 years), should be regularly screened for vitamin B12 deficiency and metformin is associated with B12 deficiency, but this is not associated with peripheral neuropathy.

Highlights

  • Metformin is the first therapeutic choice for management of type 2 diabetes mellitus (T2DM), as recommended by the American Diabetes Association and the European Association for the Study of Diabetes

  • The odds ratio for serum vitamin B12 deficiency in metformin users was 4.72

  • There were no significant differences in a test of peripheral neuropathy between the metformin users and non-metformin users (P > 0.05)

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Summary

Introduction

Metformin is the first therapeutic choice for management of type 2 diabetes mellitus (T2DM), as recommended by the American Diabetes Association and the European Association for the Study of Diabetes. Several studies have shown that long-term use of metformin leads to malabsorption of vitamin B12, with a decrease in the concentration of serum vitamin B12 from 30% to 14% [6]. Randomized control trials and cross-sectional studies have reported a decrease in serum vitamin B12 level between 9% and 52% with metformin use [5, 7]. A systematic review by Chapman et al (2016) of individuals with T2DM found 10 out of 17 observational studies reported that metformin users had significantly lower levels of vitamin B12 than non-metformin users. A metaanalysis within this review of four clinical trials demonstrated that metformin significantly reduced overall vitamin B12 levels after three to six months of use [8]

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