胰高血糖素样肽-1受体激动剂（GLP-1RAs）、钠-葡萄糖协同转运蛋白2抑制剂（SGLT2is）和非甾体盐皮质激素受体拮抗剂（nsMRAs）对2型糖尿病合并慢性肾脏病患者心血管和肾脏结局的疗效与安全性：一项系统评价和网络荟萃分析。
完整摘要 · 中文译文
目的：通过网络荟萃分析比较GLP-1受体激动剂（GLP-1RAs）、SGLT2抑制剂（SGLT2is）和非甾体盐皮质激素受体拮抗剂（nsMRAs）在2型糖尿病合并慢性肾脏病（T2D-CKD）中的心血管和肾脏获益及安全性。 方法：系统检索截至2026年8月7日发表的随机对照试验（RCT）。采用频率学随机效应网络荟萃分析。使用CINeMA评估证据确定性。 结果：共纳入21项RCT，涉及51,899例患者。与安慰剂相比，nsMRAs与较低的肾脏主要复合结局和心力衰竭住院（HHF）风险相关，而SGLT2is与较低的主要不良心血管事件（MACE）、肾脏主要复合结局和HHF风险相关。GLP-1RAs与较低的MACE、肾脏主要复合结局、HHF、全因死亡和心血管死亡风险相关。类别间间接比较提示，SGLT2is的肾脏主要复合结局估计风险低于GLP-1RAs（RR 0.77，95% CI 0.64-0.91）或nsMRAs（nsMRAs对比SGLT2is：RR 1.28，95% CI 1.10-1.50）。HHF的估计风险在SGLT2is中也低于nsMRAs（nsMRAs对比SGLT2is：RR 1.28，95% CI 1.01-1.63）。对于心血管死亡，间接估计提示GLP-1RAs的风险低于SGLT2is（SGLT2is对比GLP-1RAs：RR 1.28，95% CI 1.03-1.58），而nsMRAs与GLP-1RAs的比较未达到统计学显著性（RR 1.24，95% CI 0.99-1.56）。MACE或全因死亡未发现具有统计学显著性的类别间差异。所有类别间比较均基于排 仅依赖于间接证据。安全性分析显示，与安慰剂相比，nsMRA的高钾血症风险和SGLT2i的生殖器感染风险更高。敏感性分析大体上支持主要发现。证据的可信度大多为低到中等，主要原因是间接性。 结论：在T2D-CKD患者中，与安慰剂相比，这三类药物均减少了若干心肾结局。类间间接比较提示，在部分比较中，SGLT2i对主要肾脏结局和HHF的相对效应估计更有利，而GLP-1RA对心血管死亡的相对效应估计更有利。MACE方面未观察到明确的类间差异。由于网络中缺乏活性药物类别之间的头对头比较，这些发现和治疗排序应谨慎解读。需要直接比较和联合治疗试验来指导个体化治疗选择。 系统综述注册：https://www.crd.york.ac.uk/PROSPERO/view/CRD420251150683，标识符CRD420251150683。
完整摘要 · 英文原文
OBJECTIVE: To compare cardiovascular and renal benefits and safety of GLP-1RAs, SGLT2is, and nsMRAs in T2D-CKD using network meta-analysis. METHODS: RCTs published through 7 August 2026 were systematically identified. A frequentist random-effects network meta-analysis was performed. Evidence certainty was assessed with CINeMA. RESULTS: A total of 21 RCTs involving 51,899 patients were included. Compared with placebo, nsMRAs were associated with lower risks of the major kidney composite outcome and hospitalization for heart failure (HHF), whereas SGLT2is were associated with lower risks of major adverse cardiovascular events (MACE), the major kidney composite outcome, and HHF. GLP-1RAs were associated with lower risks of MACE, the major kidney composite outcome, HHF, all-cause mortality, and cardiovascular death. Between-class indirect comparisons suggested a lower estimated risk of the major kidney composite outcome with SGLT2is than with GLP-1RAs (RR 0.77, 95% CI 0.64-0.91) or nsMRAs (nsMRAs versus SGLT2is: RR 1.28, 95% CI 1.10-1.50). The estimated risk of HHF was also lower with SGLT2is than with nsMRAs (nsMRAs versus SGLT2is: RR 1.28, 95% CI 1.01-1.63). For cardiovascular death, the indirect estimate suggested a lower risk with GLP-1RAs than with SGLT2is (SGLT2is versus GLP-1RAs: RR 1.28, 95% CI 1.03-1.58), whereas the comparison between nsMRAs and GLP-1RAs did not reach statistical significance (RR 1.24, 95% CI 0.99-1.56). No statistically significant between-class differences were identified for MACE or all-cause mortality. All between-class comparisons were based exclusively on indirect evidence. Safety analyses showed higher risks of hyperkalemia with nsMRAs and genital infections with SGLT2is than with placebo. Sensitivity analyses broadly supported the main findings. Confidence in the evidence was mostly low to moderate, primarily because of indirectness. CONCLUSION: In patients with T2D-CKD, all three drug classes reduced several cardiorenal outcomes versus placebo. Between-class indirect comparisons suggested more favorable relative-effect estimates for SGLT2is on major kidney outcomes and HHF in selected comparisons, and for GLP-1RAs on cardiovascular death. No clear between-class difference was observed for MACE. Because the network lacked head-to-head comparisons between active drug classes, these findings and treatment rankings should be interpreted cautiously. Direct comparative and combination-therapy trials are needed to guide individualized treatment selection. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251150683, identifier CRD420251150683.