Abstract
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.
Highlights
Metformin, a first-line drug for type 2 diabetes mellitus (T2DM) recommended by most guidelines of diabetes, is widely used in patients with polycystic ovary syndrome (PCOS), pre-diabetes, and other diseases involving insulin resistance [1,2]
Metformin and Homocysteine results of the analysis showed that metformin did not have a statistically significant Metformin andoverall
The subgroup analyses noted that metformin administration was associated with elevation of Hcy in the patients without supplementation of folic acid or B-group vitamins, which indicated that metformin might induce
Summary
A first-line drug for type 2 diabetes mellitus (T2DM) recommended by most guidelines of diabetes, is widely used in patients with polycystic ovary syndrome (PCOS), pre-diabetes, and other diseases involving insulin resistance [1,2]. Vitamin B12 deficiency was noted to be a potential disadvantage of metformin by the latest American Diabetes Association (ADA) guidelines [1]. A previous meta-analysis demonstrated that metformin treatment was associated with a decreased concentration of serum Vitamin B12 in a dose-dependent manner [3]. The accumulation of Hcy, known as hyperhomocysteinemia (HHcy), is often resulted from Vitamin B12 deficiency [4], and is associated with an increased risk of cardiovascular diseases, cognitive impairment, cancer, chronic renal failure and other chronic diseases [4,5,6,7,8,9,10,11]. No consensus was reached on whether metformin could induce Hcy elevation. 3 months enzyme-linked immunoassay and an automated fluorescence polarization analyzer
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