The efficacy of vitamin B12 supplementation for treating vitamin B12 deficiency and peripheral neuropathy in metformin-treated type 2 diabetes mellitus patients: A systematic review

Diabetes Metab Syndr. 2022 Oct;16(10):102634. doi: 10.1016/j.dsx.2022.102634. Epub 2022 Oct 2.

Abstract

Background and aims: Metformin-treated type 2 diabetes mellitus (T2DM) patients are at higher risk of vitamin B12 deficiency and more severe neuropathy symptoms. There is still no guideline suggesting vitamin B12 supplementation for this population. This study aimed to analyze the efficacy of vitamin B12 supplementation in this population.

Method: Studies reporting the efficacy of vitamin B12 supplementation in metformin-treated T2DM patients were systematically searched in PubMed, Cochrane, EBSCOHost, and Scopus following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Additional relevant studies were searched manually through citations. Study quality and risk of bias were assessed using suitable tools.

Results: Seven clinical trials with a total of 506 participants were included. Using the Cochrane's Risk of Bias 2 tools for clinical trials, 4 studies were assessed to have high risk of bias and 3 studies had low risk of bias. There were 5 studies that measured changes in serum vitamin B12 level, all of which reported a statistically significant increase after supplementation. Significant reductions in homocysteine after supplementation were found in 2 studies. Its effect on neuropathy symptoms was still unclear, with 2 studies reporting a significant improvement and 1 study reporting no significant effect.

Conclusions: The results of this systematic review support the implementation of vitamin B12 supplementation for metformin-treated T2DM to prevent or treat vitamin B12 deficiency and neuropathy. More high-quality clinical studies are required to generate quantitative analysis and to encourage supplementation in available guidelines.

Keywords: (S): type 2 diabetes mellitus; Metformin; Peripheral neuropathy; Vitamin B(12) deficiency; Vitamin B(12) supplementation.

Publication types

  • Systematic Review
  • Review

MeSH terms

  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Dietary Supplements
  • Homocysteine
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Metformin* / therapeutic use
  • Peripheral Nervous System Diseases*
  • Vitamin B 12 / therapeutic use
  • Vitamin B 12 Deficiency* / drug therapy
  • Vitamin B 12 Deficiency* / etiology
  • Vitamins / therapeutic use

Substances

  • Metformin
  • Vitamin B 12
  • Hypoglycemic Agents
  • Homocysteine
  • Vitamins