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

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.