临床荟萃 ›› 2026, Vol. 41 ›› Issue (8): 677-684.doi: 10.3969/j.issn.1004-583X.2026.08.001
• 循证研究 • 下一篇
周域, 邓丽平(
), 胡俊, 寿玥莺, 吴勐, 高洁婷, 李韦
收稿日期:2026-04-21
出版日期:2026-08-20
发布日期:2026-08-25
通讯作者:
邓丽平
E-mail:1473040098@qq.com
Zhou Yu, Deng Liping(
), Hu Jun, Shou Yueying, Wu Meng, Gao Jieting, Li Wei
Received:2026-04-21
Online:2026-08-20
Published:2026-08-25
Contact:
Deng Liping
E-mail:1473040098@qq.com
摘要:
目的 使用网状meta分析评价5种钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂致2型糖尿病患者发生尿路感染的风险。方法 检索中、英文数据库获取关于恩格列净、达格列净、卡格列净、恒格列净、艾托格列净治疗2型糖尿病出现尿路感染的随机对照试验(RCT),检索时限为建库至2026年2月28日。通过对文献进行筛选、数据提取、由Cochrane系统手册进行纳入文献质量评价,采用Revman5.3、Stata15.1进行网状meta分析。结果 共纳入20个RCT、涉及19种干预措施。网状meta分析结果显示:15 mg艾托格列净与安慰剂相比致使患者发生尿路感染的风险较低;15 mg艾托格列净引起患者尿路感染的风险分别低于100 mg卡格列净、5 mg达格列净、10 mg恩格列净、10 mg达格列净、300 mg卡格列净;5 mg艾托格列净发生尿路感染的风险低于300 mg卡格列净;其他各干预措施间相比,差异无统计学意义。网状meta分析排序结果显示,发生尿路感染的风险从低到高排序为:25 mg艾托格列净<15 mg艾托格列净<5 mg恒格列净<10 mg恒格列净<5 mg艾托格列净<1 mg艾托格列净<1 mg恩格列净<1 mg达格列净<安慰剂<2.5 mg达格列净<25 mg恩格列净<50 mg恩格列净<5 mg恩格列净<100 mg卡格列净<5 mg达格列净<10 mg恩格列净<10 mg艾托格列净<10 mg达格列净<300 mg卡格列净。发表偏倚分析结果显示,本研究存在发表偏倚的可能性较低。结论 从降低临床尿路感染发生率出发,安全性较高的有25 mg艾托格列净、15 mg艾托格列净、5 mg恒格列净。
中图分类号:
周域, 邓丽平, 胡俊, 寿玥莺, 吴勐, 高洁婷, 李韦. 不同剂量SGLT-2抑制剂致2型糖尿病患者尿路感染风险的网状meta分析[J]. 临床荟萃, 2026, 41(8): 677-684.
Zhou Yu, Deng Liping, Hu Jun, Shou Yueying, Wu Meng, Gao Jieting, Li Wei. Network meta-analysis of the risk of urinary tract infection in patients with type 2 diabetes mellitus treated with different doses of SGLT-2 inhibitors[J]. Clinical Focus, 2026, 41(8): 677-684.
| 纳入研究 | 样本量 (例) | 试验组 | 对照组 | 基础治疗 | 疗程 (周) | 病程 (年) | 随访时间 (周) | 平均年龄 (岁) |
|---|---|---|---|---|---|---|---|---|
| Weng 2021[ | 483 | 恒格列净5 mg | 安慰剂 | 二甲双胍 | 24 | / | 4 | 55 |
| 恒格列净10 mg | ||||||||
| Ferrannini 2013[ | 326 | 恩格列净5 mg | 安慰剂 | 无 | 12 | / | / | 58 |
| 恩格列净10 mg | ||||||||
| 恩格列净25 mg | ||||||||
| Yale 2017[ | 215 | 卡格列净100 mg | 安慰剂 | 无 | 18 | 10 | 52 | 65 |
| 卡格列净300 mg | ||||||||
| Strojek 2014[ | 596 | 达格列净2.5 mg | 安慰剂 | 格列美脲 | 48 | 7 | / | 60 |
| 达格列净5 mg | ||||||||
| 达格列净10 mg | ||||||||
| Wilding2014[ | 800 | 达格列净2.5 mg | 安慰剂 | 胰岛素 | 24 | 14 | 104 | 60 |
| 达格列净5 mg | ||||||||
| 达格列净10 mg | ||||||||
| Kaku 2013[ | 279 | 达格列净1 mg | 安慰剂 | 无 | 12 | 5 | / | 57 |
| 达格列净2.5 mg | ||||||||
| 达格列净5 mg | ||||||||
| 达格列净10 mg | ||||||||
| Rosenstock 2013[ | 424 | 恩格列净1 mg | 安慰剂 | 二甲双胍 | 12 | / | / | 59 |
| 恩格列净5 mg | ||||||||
| 恩格列净10 mg | ||||||||
| 恩格列净25 mg | ||||||||
| 恩格列净50 mg | ||||||||
| Amin 2015[ | 273 | 艾托格列净1 mg | 安慰剂 | 无 | 12 | 23 | / | 55 |
| 艾托格列净5 mg | ||||||||
| 艾托格列净10 mg | ||||||||
| 艾托格列净25 mg | ||||||||
| Wilding 2013[ | 469 | 达格列净2.5 mg | 安慰剂 | 无 | 26 | 10 | / | 57 |
| 达格列净5 mg | ||||||||
| 达格列净10 mg | ||||||||
| Yamout 2014[ | 1085 | 卡格列净100 mg | 安慰剂 | 无 | 12 | 15 | / | 67 |
| 卡格列净300 mg | ||||||||
| Stenlof 2013[ | 584 | 卡格列净100 mg | 安慰剂 | 无 | 26 | 4 | / | 55 |
| 卡格列净300 mg | ||||||||
| Yale 2014[ | 269 | 卡格列净100 mg | 安慰剂 | 无 | 52 | / | / | 69 |
| 卡格列净300 mg | ||||||||
| Bode 2013[ | 714 | 卡格列净100 mg | 安慰剂 | 无 | 26 | 12 | / | 64 |
| 卡格列净300 mg | ||||||||
| Yang 2016[ | 449 | 达格列净5 mg | 安慰剂 | 二甲双胍 | 24 | 5 | / | 53 |
| 达格列净10 mg | ||||||||
| Liu 2020[ | 455 | 艾托格列净5 mg | 安慰剂 | 格列美脲 | 52 | 8 | / | 56 |
| 艾托格列净15 mg | ||||||||
| Kovacs 2014[ | 498 | 恩格列净10 mg | 安慰剂 | 吡格列酮±二甲双胍 | 24 | / | / | 54 |
| 恩格列净25 mg | ||||||||
| Rosenstock 2014[ | 563 | 恩格列净10 mg | 安慰剂 | 胰岛素 | 52 | / | / | / |
| 恩格列净25 mg | ||||||||
| Strojek 2011[ | 438 | 达格列净2.5 mg | 安慰剂 | 格列美脲 | 24 | 7 | / | 60 |
| 达格列净5 mg | ||||||||
| 达格列净10 mg | ||||||||
| Terra 2017[ | 461 | 艾托格列净5 mg | 安慰剂 | 无 | 52 | 5 | / | 56 |
| 艾托格列净15 mg | ||||||||
| Ji 2019[ | 506 | 艾托格列净5 mg | 安慰剂 | 二甲双胍 | 26 | 7 | / | 56 |
| 艾托格列净15 mg |
表1 纳入文献基本特征
Tab.1 Basic characteristics of the included studies
| 纳入研究 | 样本量 (例) | 试验组 | 对照组 | 基础治疗 | 疗程 (周) | 病程 (年) | 随访时间 (周) | 平均年龄 (岁) |
|---|---|---|---|---|---|---|---|---|
| Weng 2021[ | 483 | 恒格列净5 mg | 安慰剂 | 二甲双胍 | 24 | / | 4 | 55 |
| 恒格列净10 mg | ||||||||
| Ferrannini 2013[ | 326 | 恩格列净5 mg | 安慰剂 | 无 | 12 | / | / | 58 |
| 恩格列净10 mg | ||||||||
| 恩格列净25 mg | ||||||||
| Yale 2017[ | 215 | 卡格列净100 mg | 安慰剂 | 无 | 18 | 10 | 52 | 65 |
| 卡格列净300 mg | ||||||||
| Strojek 2014[ | 596 | 达格列净2.5 mg | 安慰剂 | 格列美脲 | 48 | 7 | / | 60 |
| 达格列净5 mg | ||||||||
| 达格列净10 mg | ||||||||
| Wilding2014[ | 800 | 达格列净2.5 mg | 安慰剂 | 胰岛素 | 24 | 14 | 104 | 60 |
| 达格列净5 mg | ||||||||
| 达格列净10 mg | ||||||||
| Kaku 2013[ | 279 | 达格列净1 mg | 安慰剂 | 无 | 12 | 5 | / | 57 |
| 达格列净2.5 mg | ||||||||
| 达格列净5 mg | ||||||||
| 达格列净10 mg | ||||||||
| Rosenstock 2013[ | 424 | 恩格列净1 mg | 安慰剂 | 二甲双胍 | 12 | / | / | 59 |
| 恩格列净5 mg | ||||||||
| 恩格列净10 mg | ||||||||
| 恩格列净25 mg | ||||||||
| 恩格列净50 mg | ||||||||
| Amin 2015[ | 273 | 艾托格列净1 mg | 安慰剂 | 无 | 12 | 23 | / | 55 |
| 艾托格列净5 mg | ||||||||
| 艾托格列净10 mg | ||||||||
| 艾托格列净25 mg | ||||||||
| Wilding 2013[ | 469 | 达格列净2.5 mg | 安慰剂 | 无 | 26 | 10 | / | 57 |
| 达格列净5 mg | ||||||||
| 达格列净10 mg | ||||||||
| Yamout 2014[ | 1085 | 卡格列净100 mg | 安慰剂 | 无 | 12 | 15 | / | 67 |
| 卡格列净300 mg | ||||||||
| Stenlof 2013[ | 584 | 卡格列净100 mg | 安慰剂 | 无 | 26 | 4 | / | 55 |
| 卡格列净300 mg | ||||||||
| Yale 2014[ | 269 | 卡格列净100 mg | 安慰剂 | 无 | 52 | / | / | 69 |
| 卡格列净300 mg | ||||||||
| Bode 2013[ | 714 | 卡格列净100 mg | 安慰剂 | 无 | 26 | 12 | / | 64 |
| 卡格列净300 mg | ||||||||
| Yang 2016[ | 449 | 达格列净5 mg | 安慰剂 | 二甲双胍 | 24 | 5 | / | 53 |
| 达格列净10 mg | ||||||||
| Liu 2020[ | 455 | 艾托格列净5 mg | 安慰剂 | 格列美脲 | 52 | 8 | / | 56 |
| 艾托格列净15 mg | ||||||||
| Kovacs 2014[ | 498 | 恩格列净10 mg | 安慰剂 | 吡格列酮±二甲双胍 | 24 | / | / | 54 |
| 恩格列净25 mg | ||||||||
| Rosenstock 2014[ | 563 | 恩格列净10 mg | 安慰剂 | 胰岛素 | 52 | / | / | / |
| 恩格列净25 mg | ||||||||
| Strojek 2011[ | 438 | 达格列净2.5 mg | 安慰剂 | 格列美脲 | 24 | 7 | / | 60 |
| 达格列净5 mg | ||||||||
| 达格列净10 mg | ||||||||
| Terra 2017[ | 461 | 艾托格列净5 mg | 安慰剂 | 无 | 52 | 5 | / | 56 |
| 艾托格列净15 mg | ||||||||
| Ji 2019[ | 506 | 艾托格列净5 mg | 安慰剂 | 二甲双胍 | 26 | 7 | / | 56 |
| 艾托格列净15 mg |
图4 尿路感染网状meta分析联赛图[RR(95%CI )] 注:A.安慰剂;B.5 mg恩格列净;C.10 mg恩格列净;D.25 mg恩格列净;E.100 mg卡格列净;F.300 mg卡格列净;G.2.5 mg达格列净;H.5 mg达格列净;I.10 mg达格列净;J.1 mg达格列净;K.50 mg恩格列净;L.1 mg恩格列净;M.1 mg艾托格列净;N.5 mg艾托格列净;O.10 mg艾托格列净;P.25 mg艾托格列净;Q.15 mg艾托格列净;R.5 mg恒格列净;S.10 mg恒格列净。
Fig.4 League table of the network meta-analysis of urinary tract infection risk (RR[95% CI]) Note:A:Placebo;B:5 mg empagliflozin;C:10 mg empagliflozin;D:25 mg empagliflozin;E:100 mg Canagliflozin;F:300 mg Canagliflozin;G:2.5 mg Dapagliflozin;H:5 mg Dapagliflozin;I:10 mg Dapagliflozin;J:1 mg Dapagliflozin;K:50 mg empagliflozin;L:1 mg empagliflozin;M:1 mg Ertugliflozin;N:5 mg Ertugliflozin;O:10 mg Ertugliflozin;P:25 mg Ertugliflozin;Q:15 mg Ertugliflozin;R:5 mg Henagliflozin;S:10 mg Henagliflozin。
| 干预措施 | SUCRA | PrBest | MeanRank |
|---|---|---|---|
| 25 mg艾托格列净 | 89.3 | 68.8 | 2.9 |
| 15 mg艾托格列净 | 79.9 | 2.9 | 4.6 |
| 5 mg恒格列净 | 77.6 | 6.8 | 5 |
| 10 mg恒格列净 | 77.3 | 6.5 | 5.1 |
| 5 mg艾托格列净 | 66.7 | 0.3 | 7 |
| 1 mg艾托格列净 | 62.4 | 4.2 | 7.8 |
| 1 mg恩格列净 | 57.6 | 4.7 | 8.6 |
| 1 mg达格列净 | 52.6 | 0 | 9.5 |
| 安慰剂 | 47.5 | 0 | 10.5 |
| 2.5 mg达格列净 | 47.4 | 4.2 | 10.5 |
| 25 mg恩格列净 | 41.7 | 0 | 11.5 |
| 50 mg恩格列净 | 39 | 0.9 | 12 |
| 5 mg恩格列净 | 38.9 | 0.5 | 12 |
| 100 mg卡格列净 | 38.3 | 0 | 12.1 |
| 5 mg达格列净 | 31.9 | 0 | 13.3 |
| 10 mg恩格列净 | 31.5 | 0 | 13.3 |
| 10 mg艾托格列净 | 27 | 0.1 | 14.1 |
| 10 mg达格列净 | 24 | 0 | 14.7 |
| 300 mg卡格列净 | 19.7 | 0 | 15.5 |
表2 尿路感染风险排序
Tab.2 Ranking of urinary tract infection risk
| 干预措施 | SUCRA | PrBest | MeanRank |
|---|---|---|---|
| 25 mg艾托格列净 | 89.3 | 68.8 | 2.9 |
| 15 mg艾托格列净 | 79.9 | 2.9 | 4.6 |
| 5 mg恒格列净 | 77.6 | 6.8 | 5 |
| 10 mg恒格列净 | 77.3 | 6.5 | 5.1 |
| 5 mg艾托格列净 | 66.7 | 0.3 | 7 |
| 1 mg艾托格列净 | 62.4 | 4.2 | 7.8 |
| 1 mg恩格列净 | 57.6 | 4.7 | 8.6 |
| 1 mg达格列净 | 52.6 | 0 | 9.5 |
| 安慰剂 | 47.5 | 0 | 10.5 |
| 2.5 mg达格列净 | 47.4 | 4.2 | 10.5 |
| 25 mg恩格列净 | 41.7 | 0 | 11.5 |
| 50 mg恩格列净 | 39 | 0.9 | 12 |
| 5 mg恩格列净 | 38.9 | 0.5 | 12 |
| 100 mg卡格列净 | 38.3 | 0 | 12.1 |
| 5 mg达格列净 | 31.9 | 0 | 13.3 |
| 10 mg恩格列净 | 31.5 | 0 | 13.3 |
| 10 mg艾托格列净 | 27 | 0.1 | 14.1 |
| 10 mg达格列净 | 24 | 0 | 14.7 |
| 300 mg卡格列净 | 19.7 | 0 | 15.5 |
图5 尿路感染发生风险概率排序 注:A.安慰剂;B.5 mg恩格列净;C.10 mg恩格列净;D.25 mg恩格列净;E.100 mg卡格列净;F.300 mg卡格列净;G.25 mg达格列净;H.5 mg达格列净;I.10 mg达格列净;J.1 mg达格列净;K.50 mg恩格列净;L.1 mg恩格列净;M.1 mg艾托格列净;N.5 mg艾托格列净;O.10 mg艾托格列净;P.25 mg艾托格列净;Q.15 mg艾托格列净;R.5 mg恒格列净;S.10 mg恒格列净。
Fig.5 Probability ranking of urinary tract infection risk Note:A:Placebo;B:5 mg empagliflozin;C:10 mg empagliflozin;D:25 mg empagliflozin;E:100 mg Canagliflozin;F:300 mg Canagliflozin;G:2.5 mg Dapagliflozin;H:5 mg Dapagliflozin;I:10 mg Dapagliflozin;J:1 mg Dapagliflozin;K:50 mg empagliflozin;L:1 mg empagliflozin;M:1 mg Ertugliflozin;N:5 mg Ertugliflozin;O:10 mg Ertugliflozin;P:25 mg Ertugliflozin;Q:15 mg Ertugliflozin;R:5 mg Henagliflozin;S:10 mg Henagliflozin。
图6 尿路感染发生风险的漏斗图 注:此图为stata软件中命令生成的网状meta专用漏斗图,用来评估偏倚情况。$\stackrel{-}{\mathit{y}}$xy表示不同干预措施对比后得到的原始效应量,yxy表示两两比较下得到的平均效应量。横轴数值表示校正后的偏倚值,纵轴数值越小,研究精度越高。
Fig.6 Funnel plot of the risk of urinary tract infection Note:A:Placebo;B:5 mg empagliflozin;C:10 mg empagliflozin;D:25 mg empagliflozin;E:100 mg Canagliflozin;F:300 mg Canagliflozin;G:2.5 mg Dapagliflozin;H:5 mg Dapagliflozin;I:10 mg Dapagliflozin;J:1 mg Dapagliflozin;K:50 mg empagliflozin;L:1 mg empagliflozin;M:1 mg Ertugliflozin;N:5 mg Ertugliflozin;O:10 mg Ertugliflozin;P:25 mg Ertugliflozin;Q:15 mg Ertugliflozin;R:5 mg Henagliflozin;S:10 mg Henagliflozin。
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