Siddiqi Tariq Jamal, Cherney David, Siddiqui Hasan Fareed, Jafar Tazeen H, Januzzi James L, Khan Muhammad Shahzeb, Levin Adeera, Marx Nikolaus, Rangaswami Janani, Testani Jeffrey, Usman Muhammad Shariq, Wanner Christoph, Zannad Faiez, Butler Javed
Department of Medicine, Baylor University Medical Center, Dallas, Texas.
Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada.
J Am Soc Nephrol. 2025 Feb 1;36(2):242-255. doi: 10.1681/ASN.0000000000000491. Epub 2024 Sep 4.
Sodium-glucose cotransporter-2 (SGLT2) inhibitors slowed the rate of eGFR slope decline in patients with heart failure, CKD, and type 2 diabetes mellitus and in all combinations of multimorbid conditions among these diseases. SGLT2 inhibitors decreased kidney composite outcomes among all disease states and different combinations of multimorbidity, except in patients with heart failure with preserved ejection fraction and heart failure without type 2 diabetes mellitus. SGLT2 inhibitors were found to decrease the risk of kidney failure in patients with type 2 diabetes mellitus and also in those with CKD.
The effects of sodium-glucose cotransporter-2 inhibitors (SGLT2is) on kidney outcomes in patients with varying combinations of heart failure, CKD, and type 2 diabetes mellitus have not been quantified.
PubMed and Scopus were queried up to December 2023 for primary and secondary analyses of placebo-controlled trials of SGLT2is in patients with heart failure, CKD, or type 2 diabetes mellitus. Outcomes of interest were composite kidney end point (combination of eGFR <15 ml/min per 1.73 m, sustained doubling of serum creatinine, varying percent change in eGFR, and need for KRT), rate of eGFR slope decline, and albuminuria progression. Hazard ratios (HRs) and mean differences with their 95% confidence intervals (CIs) were extracted onto an Excel sheet, and the results were then pooled using a random-effect model through Review Manager (version 5.3, Cochrane Collaboration).
Eleven trials (=80,928 patients) were included. Compared with the placebo, SGLT2is reduced the risk of the composite kidney end point by 41% (HR, 0.59; 95% CI, 0.42 to 0.83) in heart failure with reduced ejection fraction, 36% (HR, 0.64; 95% CI, 0.55 to 0.73) in CKD, and 38% (HR, 0.62; 95% CI, 0.56 to 0.69) in type 2 diabetes mellitus. A similar pattern of benefit was observed in combinations of these comorbidities and in patients without baseline heart failure, CKD, or type 2 diabetes mellitus. SGLT2is slowed the rate of eGFR slope decline and reduced the risk of sustained doubling of serum creatinine by 36% (HR, 0.64; 95% CI, 0.56 to 0.72) in the overall population, and a consistent effect on kidney outcomes was observed in most subpopulations with available data.
SGLT2i improved kidney outcomes in cohorts with heart failure, CKD, and type 2 diabetes mellitus, and these effects were consistent across patients with different combinations of these comorbidities.
钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂减缓了心力衰竭、慢性肾脏病（CKD）和2型糖尿病患者以及这些疾病多种共病组合患者的估算肾小球滤过率（eGFR）斜率下降速率。SGLT2抑制剂降低了所有疾病状态和不同共病组合患者的肾脏复合结局风险，但射血分数保留的心力衰竭患者和无2型糖尿病的心力衰竭患者除外。研究发现，SGLT2抑制剂可降低2型糖尿病患者以及CKD患者的肾衰竭风险。
钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）对心力衰竭、CKD和2型糖尿病不同组合患者肾脏结局的影响尚未量化。
检索截至2023年12月的PubMed和Scopus数据库，以获取SGLT2i在心力衰竭、CKD或2型糖尿病患者中进行的安慰剂对照试验的一级和二级分析。感兴趣的结局包括复合肾脏终点（eGFR<15 ml/min/1.73 m²、血清肌酐持续翻倍、eGFR不同百分比变化以及需要进行肾脏替代治疗[KRT]）、eGFR斜率下降速率和蛋白尿进展情况。将风险比（HR）及其95%置信区间（CI）提取到Excel表格中，然后通过Review Manager（5.3版，Cochrane协作网）使用随机效应模型对结果进行汇总。
纳入了11项试验（n=80928例患者）。与安慰剂相比，SGLT2i在射血分数降低的心力衰竭患者中使复合肾脏终点风险降低41%（HR，0.59；95%CI，0.42至0.83），在CKD患者中降低36%（HR，0.64；95%CI，0.55至0.73），在2型糖尿病患者中降低38%（HR，0.62；95%CI，0.56至0.69）。在这些共病的组合中以及无基线心力衰竭、CKD或2型糖尿病的患者中也观察到了类似的获益模式。SGLT2i减缓了eGFR斜率下降速率，并使总体人群中血清肌酐持续翻倍的风险降低36%（HR，0.64；95%CI，0.56至0.72），并且在大多数有可用数据的亚组中对肾脏结局观察到了一致的效果。
SGLT2i改善了心力衰竭、CKD和2型糖尿病队列患者的肾脏结局，并且这些效应在这些共病不同组合的患者中是一致的。
