沙格列汀治疗成人2型糖尿病的有效性和安全性: 基于随机对照试验的meta分析

doi:10.5246/jcps.2016.02.014

摘要/Abstract

摘要：

二肽基肽酶Ⅳ(DDP-4)抑制剂沙格列汀是一种新型的口服降糖药物。目前对于沙格列汀联合其他口服降糖药物对于能否提高降糖效果及增加不良反应有诸多争议。本研究采用系统评价的方法探讨沙格列汀作为单药或与其他口服降糖药物联用治疗2型糖尿病的疗效和安全性,以期为其应用提供循证医学证据。计算机检索Pubmed、Embase、The Cochrane Library和临床试验注册平台(1990年1月至2013年10月),使用加权平均值分析糖化血红蛋白(HbA1c)、体重和空腹血糖的变化。使用相对危险度分析HbA1c<7%的达标率和不良反应发生率。最终纳入了来自16个随机对照试验的18篇文章以及国际临床试验注册平台的一项试验。与安慰剂组相比,沙格列汀各剂量组HbA1c均值自基线的下降显著增加(2.5 mg/d WMD = –0.45%, 95% CI, –0.48% to –0.42%; 5 mg/day WMD = –0.52%, 95% CI, –0.60% to –0.44%) , 沙格列汀联合治疗组达到HbA1c<7%的比率高于单用噻唑烷二酮、双倍剂量的格列本脲、双倍剂量的二甲双胍,而其对体重的影响是中性的。沙格列汀组低血糖(RR = 1.28, 95% CI 0.72 to 2.27,P = 0.40)和严重不良反应的发生率(RR = 1.25, 95% CI 0.94 to 1.66, P = 0.13)与对照组无差异,也未观察到沙格列汀组与对照组在感染不良发生率方面的差异。因此,沙格列汀单药或者联合治疗能有效控制2型糖尿病患者的血糖, 且低血糖和感染的不良反应发生率较低。但其远期疗效及安全性有待开展更多高质量、大样本的RCT加以验证。

关键词: 二肽基肽酶Ⅳ抑制剂, 沙格列汀, 荟萃分析, 2型糖尿病, 空腹血糖, 糖化血红蛋白, 随机随照试验, 低血糖

Abstract:

As a new oral hypoglycemic agent, saxagliptin belongs to the class of dipeptidyl peptidase-4 (DPP-4) inhibitors. However, it remains inconclusive whether saxagliptin is associated with increased risk of adverse events (AE) and efficacy as add-on treatment. Therefore, we performed an up-to-date meta-analysis to compare the efficacy and safety of saxagliptin with placebo and other oral hypoglycemic agents in adult patients with type 2 diabetes mellitus (T₂DM). Randomized clinical trials (RCTs) comparing saxagliptin with comparators were retrieved by selecting articles from Pubmed, Embase, Cochrane Library and Clinical Trials Registry Platform up to Oct. 2013. Weighted mean difference (WMD) was used to analyze the effect of hypoglycemic agents on HbA1c, weight and fasting plasma glucose (FPG). While the patients who achieved HbA1c<7.0% and had AE were analyzed as relative risks (RR).A total of 18 articles from 16 RCTs and one clinic trial from the WHO International Clinical Trials Registry Platform met the included criterion. Clinically significant decrease from baseline HbA1c compared with placebo was certified for 2.5 mg/day saxagliptin (WMD = –0.45%, 95%CI, –0.48% to –0.42%) and 5 mg/d saxagliptin (WMD = –0.52%, 95%CI, –0.60% to –0.44%). Saxagliptin as add-on therapy was superior to thiazolidinediones, up-titrated glyburide, up-titrated metformin or metformin monotherapy in achieving HbA1c<7.0%. Treatment with saxagliptin had negligible effect on weight, and it was considered weight neutral. Saxagliptin treatment did not increase the risk of hypoglycemia (RR = 1.28, 95% CI 0.72 to 2.27, P = 0.40) and serious adverse experiences (RR = 1.25, 95% CI 0.94 to 1.66, P = 0.13). No statistically significant differences were observed between saxagliptin and comparators in terms of the risk of infections.The present study showed that saxagliptinwas effective in improving glycaemic control in T₂DM with a low risk of hypoglycaemia and incidence of infections in either monotherapy or add-on treatment. This founding should be further certified by large-sample size and good-designed RCT.

Key words: DPP-4 inhibitor, Saxagliptin, Meta-analysis, Type 2 diabetes mellitus, Fasting plasma glucose, Glycosylated hemoglobin, Randomized controlled trial, Hypoglycaemia

中图分类号:

R969.3

Supporting:

姚莉, 范芳芳, 胡兰, 赵生俊, 郑丽丽. 沙格列汀治疗成人2型糖尿病的有效性和安全性: 基于随机对照试验的meta分析[J]. 中国药学(英文版), 2016, 25(2): 128-139.

Li Yao, Fangfang Fan, Lan Hu, Shengjun Zhao, Lili Zheng. Efficacy and safety of saxagliptin in patients with type 2 diabetes mellitus: a meta-analysis of randomized controlled trials[J]. Journal of Chinese Pharmaceutical Sciences, 2016, 25(2): 128-139.

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