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Metformin Treatment and Homocysteine: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

by Qianying Zhang 1,†, Sheyu Li 1,†, Ling Li 2, Qianrui Li 1, Kaiyun Ren 1, Xin Sun 2 and Jianwei Li 1,*
1
Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, China
2
Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Nutrients 2016, 8(12), 798; https://doi.org/10.3390/nu8120798
Received: 10 August 2016 / Revised: 28 November 2016 / Accepted: 2 December 2016 / Published: 9 December 2016
(This article belongs to the Special Issue B-Vitamins and One-Carbon Metabolism)
The aim of this systematic review is to assess whether metformin could change the concentration of serum homocysteine (Hcy) with and without simultaneous supplementation of B-group vitamins or folic acid. A literature search was conducted in PubMed, EmBase, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify randomized controlled trials (RCTs) reporting the concentration of serum Hcy in metformin-treated adults. Meta-analysis was applied to assess the association between metformin and the changes of Hcy concentration. Twelve publications were included in this study. In the overall analysis, metformin administration was not statistically associated with the change of Hcy when compared with the control treatment (mean difference (MD), 0.40 μmol/L; 95% confidence interval (CI), −0.07~0.87 μmol/L, p = 0.10). In the subgroup analysis, metformin was significantly associated with an increased concentration of Hcy in the absence of exogenous supplementation of folic acid or B-group vitamins (MD, 2.02 μmol/L; 95% CI, 1.37~2.67 μmol/L, p < 0.00001), but with a decreased concentration of serum Hcy in the presence of these exogenous supplementations (MD, −0.74 μmol/L; 95% CI, −1.19~−0.30 μmol/L, p = 0.001). Therefore, although the overall effect of metformin on the concentration of serum Hcy was neutral, our results suggested that metformin could increase the concentration of Hcy when exogenous B-group vitamins or folic acid supplementation was not given. View Full-Text
Keywords: metformin; homocysteine; vitamin B12; folic acid; systematic review; meta-analysis metformin; homocysteine; vitamin B12; folic acid; systematic review; meta-analysis
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Zhang, Q.; Li, S.; Li, L.; Li, Q.; Ren, K.; Sun, X.; Li, J. Metformin Treatment and Homocysteine: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients 2016, 8, 798.

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