二肽基肽酶-4抑制剂与发生上呼吸道感染风险的相关性荟萃分析

Correlation between dipeptidyl peptidase-4 inhibitors and risk of upper respiratory tract infection as adverse drug reactions:meta analysis

目的:系统评价二肽基肽酶(dipeptidyl peptidase,DPP)-4抑制剂治疗2型糖尿病与发生上呼吸道感染(upper respiratory tract infection,URTI)风险的相关性。方法:利用计算机检索EMBASE、PubMed、Cochrane图书馆临床试验资料库、维普科技期刊数据库(1989年1月-2016年2月)、中国生物医学文献数据库(1978年1月-2016年2月)、中国期刊全文数据库(中国知网,1978年1月-2016年2月)以及网上图书馆(Science and Springer Link,Nature Publishing Group,Elsevier Science-Science Direct,Wiley-Blackwell,Oxford University Press)建库至2016年2月的相关文献。按Cochrane系统评价方法筛选DPP-4抑制剂治疗2型糖尿病引起URTI的所有中文和英文随机对照试验(RCTs),纳入文献经数据提取和质量评价后,采用RevMan 5.3软件进行荟萃分析。结果:共纳入36篇文献。荟萃分析结果显示:5mg/d利格列汀引起URTI不良反应的风险低于安慰剂组,差异有统计学意义[RR=0.63,95%CI(0.46,0.86),P=0.004]。其余DPP-4抑制剂,包括西格列汀、沙格列汀、维格列汀和阿格列汀,引起URTI不良反应的风险均与安慰剂组相似,差异均无统计学意义[100mg/d西格列汀组:RR=1.21,95%CI(0.87,1.67),P=0.25;沙格列汀组:RR=1.08,95%CI(0.94,1.24),P=0.29;100 mg/d维格列汀组:RR=0.62,95%CI(0.16,2.34),P=0.48;阿格列汀组:RR=0.71,95%CI(0.47,1.06),P=0.09]。结论:DPP-4抑制剂不增加URTI不良反应的风险。但其远期安全性须进行更多大样本、高质量、长期随访的随机对照试验加以验证。

Objective： To systematically evaluate the correlation between dipeptidyl peptidase（DPP）-4 inhibitors and risk of upper respiratory tract infection （URTI） in type 2 diabetes patients. Methods： The databases as EMBASE, PubMed, the Cochrane Library, the VIP China Science and Technology Journal Database（from January 1989 to February 2016）, the Chinese Biomedical Literature Database（CBM, from January 1978 to February 2016）, the Chinese Journal Full-text Database in China National Knowledge Infrastructure（CNKI, from January 1978 to February 2016）, Online libraries （Science and Springer Link, Nature Publishing Group,Elsevier Science-Science Direct,Wiley-Blackwell,Oxford University Press,until February 2016） were searched for related literature. The randomized controlled trails（RCTs） about URTI induced by DPP-4 inhibitors in the treat- ment of type 2 diabetes were collected and the quality of included RCTs was assessed according to the Cochrane collaboration system review,and then meta-analysis was performed by using RevMan 5.3 software. Results： A total of 36 RCTs were included. Meta-analysis showed that the 5 mg/d linagliptin group had lower risk of URTI than that of the placebo group（RR= 0.63, 95%CI 0.46 to 0. 86, P = 0. 004）. The other DPP-4 inhibitors including sitagliptin, saxagliptin, vildagliptin and alogliptin showed no significant differences compared with that of the placebo group （100 mg/d sitagliptin： RR= 1.21, 95% CI 0. 87- 1.67,P=0.25 ;saxagliptin： RR：I. 08,95%CI 0.94-1.24,P=0.29 ;100 mg/d vildagliptin;RR= 0.62, 95%CI 0.16-2. 34,P= 0.48 ;alogliptin： RR= 0.71,95 %CI 0. 47-1. 06,P= 0.09）. Conclusion： DPP-4 inhihitors do not increase the risk of URTI, but its long-term safety remained to be confirmed by performing more high quality,large-sample RCTs with long-term follow-ups.