胰升血糖素样肽1类似物与胰岛素治疗口服药效果不佳的2型糖尿患者的疗效和安全性的Meta分析

　　王溢苏 李伶 杨刚毅 李生兵

　　【摘要】 目的 评价胰升血糖素样肽1(GLP-1)类似物与胰岛素对于治疗口服药后效果不佳的T2DM患者的疗效及安全性。 方法 检索1990至2010年10月Medline、Embase及Cochrane相关文献，采用的关键词为“GLP-1类似物、胰岛素、T2DM、临床试验”。评价结局指标包括HbA1c、体重变化、FPG、低血糖事件、不良反应等，应用Meta分析以加权均数差(WMD)或比值比(OR)为效应量进行合并分析。 结果 纳入的8个RCT(n=2782)总体质量较高，均为平行开放标签试验。随机效应Meta分析结果显示，GLP-1类似物与胰岛素比较，HbA1c、体重平均差值(95%置信区间)分别下降0.14% (-0.27 ～-0.02)、4.38kg (-4.64～-4.11)、FPG增加2.17mmol/l (2.10 ～2.24); GLP-1类似物组餐后血糖下降超过胰岛素组。GLP-1类似物组总体低血糖事件少于胰岛素组(MH-OR 0.45[0.27,0.76]; P<0.01);两组严重低血糖事件差异无显著性意义[MH-OR 0.65(0.29,1.45)，P=0.29]。GLP-1组胃肠道反应明显增高[MH-OR 15.00;95%(5.44,41.35)，P<0.01]。 结论 GLP-1类似物是一种受到青睐的新药，但不可替代胰岛素, 尤其在降低FPG方面。

　　【关键词】GLP-1类似物;胰岛素;糖尿病，2型;临床试验

　　A meta-analysis on the effect and safety of GLP-1 analogue and insulin in inadequately controlled T2DM patients: a report of clinical trials  WANG Yi-su, LI Ling, YANG Gang-yi, et al. Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China

　　Corresponding author: YANG Gangyi, E-mail: gangyiyang@yahoo.com.cn

　　【Abstract】 Objective To compare the effect and safety of glucagons-like peptide 1 (GLP-1) analogue and insulin therapy in T2DM patients inadequately controlled with metformin and/or sulfonylurea. Methods A systematic literature search on Medline, Embase and Cochrane for randomized controlled trials was conducted by using specific search terms as“GLP-1 analogue，insulin，T2DM，clinical trials”. The literature on the subject from 1990 to October 2010 was retrieved. Of the 932 studies, 8 qualified ones were enrolled for analyses. Data on the mean change in HbA1c, weight loss, FPG, incidence of hypoglycemia, and gastrointestinal adverse events were extracted from each study and pooled for meta-analysis. Result Data from eight RCTs involving 2782 patients were pooled using a random-effect model. The mean net change (95% confidence interval) for HbA1c and weight loss for patients treated with GLP-1 analogue as compared with insulin was 0.14% (-0.27 to -0.02) and 4.38kg (-4.64 to -4.11) in decrease respectively, while FPG was 2.17mmol/L (2.10 to 2.24) in increase. The GLP-1 group showed a greater reduction in PPG than the insulin group. Overall hypoglycemia events in the GLP-1 group were less than in the insulin group (MH-OR 0.45 [0.27, 0.76], P<0.01), while there was no significant difference in the occurrence of severe hypoglycemia (MH-OR 0.65 [0.29, 1.45], P=0.29). A significantly higher number of gastrointestinal adverse events were reported in the GLP-1 group (MH-OR 15.00; 95% [5.44, 41.35], P<0.01). Conclusions GLP-1 analogue is a favorite new drug, but not a substitute of insulin, especially in reducing FPG.

　　【Keywords】 GLP-1 analogue; Insulin; Diabetes mellitus, Type 2; Clinical trials