School of Public Health, Guangxi Medical University, Nanning, Guangxi, China.
Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Clin J Am Soc Nephrol. 2020 Dec 31;16(1):70-78. doi: 10.2215/CJN.11220720. Epub 2020 Dec 29.
Little is known about the comparative effects of dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), or sodium glucose cotransporter-2 (SGLT2) inhibitors on risk of AKI. This study aimed to compare the effects of these three novel classes of glucose-lowering drugs on AKI risk in patients with or without type 2 diabetes, by network meta-analysis of event-driven cardiovascular or kidney outcome trials.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We systematically searched electronic databases up to September 2020, and included 20 event-driven cardiovascular or kidney outcome trials (18 trials included patients with type 2 diabetes only, and two trials included patients with or without type 2 diabetes). A network meta-analysis using a frequentist approach was performed to compare the effects of DPP-4 inhibitors, GLP-1RAs, or SGLT2 inhibitors on risk of AKI, and estimate the probability for each intervention as the safest one. The primary analysis included 18 trials with type 2 diabetes only, and a secondary analysis included 20 trials.
In the 18 trials with a total of 2051 AKI events (range: 1-300) among 156,690 patients with type 2 diabetes only, our network meta-analysis showed that SGLT2 inhibitors were associated with a lower risk of AKI compared with placebo (odds ratio, 0.76; 95% confidence interval, 0.66 to 0.88), whereas both DPP-4 inhibitors and GLP-1RAs had neutral effects on risk of AKI. Moreover, SGLT2 inhibitors were significantly associated with a lower risk in AKI than both GLP-1RAs (odds ratio, 0.79; 95% confidence interval, 0.65 to 0.97) and DPP-4 inhibitors (odds ratio, 0.68; 95% confidence interval, 0.54 to 0.86). SGLT2 inhibitors have the highest probability of being the safest intervention (84%). The results were similar in the secondary analysis.
Current evidence indicates that SGLT2 inhibitors have a lower risk of AKI than both DPP-4 inhibitors and GLP-1RAs.
关于二肽基肽酶-4（DPP-4）抑制剂、胰高血糖素样肽-1 受体激动剂（GLP-1RAs）或钠-葡萄糖协同转运蛋白 2（SGLT2）抑制剂对急性肾损伤（AKI）风险的比较影响，目前所知甚少。本研究旨在通过对事件驱动的心血管或肾脏结局试验的网络荟萃分析，比较这三类新型降糖药物在伴或不伴 2 型糖尿病患者中的 AKI 风险。
设计、设置、参与者和测量：我们系统地检索了电子数据库，截止到 2020 年 9 月，并纳入了 20 项事件驱动的心血管或肾脏结局试验（18 项试验仅纳入了 2 型糖尿病患者，两项试验纳入了伴或不伴 2 型糖尿病患者）。采用贝叶斯方法进行网络荟萃分析，比较 DPP-4 抑制剂、GLP-1RAs 或 SGLT2 抑制剂对 AKI 风险的影响，并估计每种干预措施作为最安全措施的概率。主要分析纳入了 18 项仅纳入 2 型糖尿病患者的试验，次要分析纳入了 20 项试验。
在 18 项仅纳入 156690 例 2 型糖尿病患者、共发生 2051 例 AKI 事件（范围为 1-300）的试验中，我们的网络荟萃分析显示，与安慰剂相比，SGLT2 抑制剂与 AKI 风险降低相关（比值比，0.76；95%置信区间，0.66 至 0.88），而 DPP-4 抑制剂和 GLP-1RAs 对 AKI 风险无影响。此外，SGLT2 抑制剂与 GLP-1RAs（比值比，0.79；95%置信区间，0.65 至 0.97）和 DPP-4 抑制剂（比值比，0.68；95%置信区间，0.54 至 0.86）相比，AKI 风险显著降低。SGLT2 抑制剂具有成为最安全干预措施的最高概率（84%）。次要分析结果相似。
目前的证据表明，与 DPP-4 抑制剂和 GLP-1RAs 相比，SGLT2 抑制剂降低 AKI 风险的效果更优。
