二甲双胍对2型糖尿病患者血清维生素B_(12)水平影响的Meta分析

Effect of metformin on serum vitamin B_(12) level in patients with type 2 diabetes mellitus:a meta analysis

目的系统评价二甲双胍对2型糖尿病患者血清维生素B12、叶酸及同型半胱氨酸水平的影响。方法计算机检索Cochrane Library、EMbase、PubMed、CBM、CNKI、VIP和万方数据库,搜集二甲双胍与2型糖尿病患者血清维生素B12水平相关的随机对照试验(RCT)。由2位研究者独立筛选文献、评价纳入研究的偏倚风险、提取数据。采用RevMan5.3软件进行Meta分析。结果共纳入5个RCT,二甲双胍组血清维生素B12水平较安慰剂组明显降低[MD=-55.86,95%CI(-86.89,-24.84),P=0.000 4];亚组分析显示血清维生素B12水平与糖尿病病程、二甲双胍使用时间及剂量呈负相关;二甲双胍组血清同型半胱氨酸(Hcy)水平较安慰剂组升高[MD=2.44,95%CI(1.41,3.46),P<0.01];两组血清叶酸水平的差异无统计学意义[MD=-2.39,95%CI(-4.93,0.15),P=0.06];二甲双胍组不良反应发生率高于安慰剂组[RR=2.0,95%CI(1.32,3.03),P=0.001]。结论二甲双胍治疗2型糖尿病患者可引起血清维生素B12水平降低、Hcy水平升高,对叶酸水平无明显影响,患者不良反应发生率较高。

Objective To systematically evaluate the effects of metformin on serum vitamin B12, folie acid and homocysteine （Hcy） levels in the patients with type 2 diabetes mellitus （T2DM）. Methods The databases of Cochrane Library, EMbase, PubMed,CBM,CNKI,VIP and Wanfang were retrieved by computer to collect the randomized controlled trials （RCTs） on the association between metformin and serum vitamin B12 level in T2DM patients. Two researchers independently screened the literatures, assessed the risk of bias of included RCTs and extracted the data. The RevMan5.3 software was used for conducting the meta anal- ysis. Results A total of 5 RCTs were included. The Meta-analysis results showed that serum vitamin B12 level in the metformin group was significantly decreased compared with the placebo group （MD= - 55.86,95 % CI（ - 86.89, - 24.84）, P = 0. 000 4） ; the subgroup analysis showed that serum vitamin B12 level was negatively correlated with the duration of diabetes,metformin use time and dose. The serum Hcy level in the metformin group was increased compared with the placebo group （MD=2.44,95%CI（1.41, 3.46）, P〈0.01） ;the serum folic acid level had no statistical differences between the two groups [MD= -2.39,95 % CI （- 4.93, 0.15）,P=0.06];the incidence rate of adverse reactions in the metformin group was higher than that in the placebo group[RR= 2.0,95%CI（1.32,3.03） ,P=0.001]. Conclusion Metformin treatment may lead to decrease of serum vitamin Pa2 level and increase of Hcy level while has no obvious influence on the folic acid level in T2DM patients, but has higher incidence rate of adverse reactions.