Table_1_Finerenone in type 2 diabetes and renal outcomes: A random-effects model meta-analysis.docx

BackgroundThe nonsteroidal mineralocorticoid antagonist finerenone is a new addition to the list of agents (angiotensin converting enzyme inhibitors and sodium glucose cotransporter 2 inhibitors) conferring renal protection to patients with diabetic kidney disease. Two recent meta-analyses using the fixed effect model in patients with chronic kidney disease (both diabetic and nondiabetic populations) came to a conflicting conclusion on the effect of finerenone on eGFR decline. This meta-analysis was undertaken exclusively in the type 2 diabetes (T2D) population to explore the robustness and heterogeneity of the effect size by conducting a random effects model meta-analysis along with draft plots and prediction intervals.
Materials and methodsA database search was conducted using the Cochrane library, PubMed, and Embase to identify relevant citations. Analysis was conducted on the 14th of September 2022, using RevMan 5.4.1 and RStudio (2022.07.1, Build 554). The hazard ratio was used as the effect size for the renal composite, while the standardized mean difference (SMD) was used to estimate the effect size of eGFR decline and reduction in the urine albumin creatinine ratio (UACR). The Cochrane risk-of-bias was used to assess the quality of the studies. The primary outcome assessed was the renal composite defined as kidney failure, a sustained decrease of at least 40% in the eGFR from baseline, or death from renal causes.
ResultsA pooled population of 13,943 patients from four citations was included for analysis. The Cochrane risk of bias was used to assess the quality of the studies. There was a significant 16% reduction in the renal composite (kidney failure, a sustained decrease of at least 40% in the eGFR from baseline, or death from renal causes) [HR: 0.84, 95% CI 0.77-0.92, 2: 0, I2: 0%). Finerenone was also associated with reduction in UACR (SMD: -0.49, 95% CI -0.53 to -0.46, τ2: < 0.0001, I2: 0%, prediction interval: -0.57 to -0.41) and prevention of decline in eGFR (SMD: -0.32, 95% CI -0.37 to -0.27, τ2: < 0.0001, I2: 0%, prediction interval: -0.43 to -0.21) without any evidence for significant heterogeneity. Except for an increase in hyperkalaemia (RR: 2.22, 95% CI 1.93-2.24), adverse events were observed with fineronone compared to placebo (RR: 1.00, 95% CI 0.98-1.01).
ConclusionThere are significant benefits in renal outcomes associated with finerenone treatment in T2D patients with established chronic kidney disease with a side effect profile comparable to placebo.

背景 非甾体类盐皮质激素受体拮抗剂（nonsteroidal mineralocorticoid antagonist）非奈利酮（finerenone）是可为糖尿病肾病患者提供肾脏保护的药物（包括血管紧张素转换酶抑制剂与钠-葡萄糖协同转运蛋白2抑制剂）中的新增药物。此前两项针对慢性肾病（涵盖糖尿病肾病与非糖尿病肾病人群）采用固定效应模型开展的荟萃分析，就非奈利酮对估算肾小球滤过率（estimated glomerular filtration rate, eGFR）下降的影响得出了相悖的结论。本研究仅纳入2型糖尿病（type 2 diabetes, T2D）人群，通过随机效应模型荟萃分析、绘图及预测区间，探究效应量的稳健性与异质性。
材料与方法 本研究通过Cochrane图书馆、PubMed及Embase数据库检索相关文献。分析于2022年9月14日开展，采用RevMan 5.4.1与RStudio（2022.07.1, Build 554）完成。肾脏复合终点的效应量采用风险比（hazard ratio, HR）表示，估算肾小球滤过率下降及尿白蛋白肌酐比值（urine albumin creatinine ratio, UACR）降低的效应量采用标准化均数差（SMD）评估。采用Cochrane偏倚风险工具评估纳入研究的质量。本研究的主要结局为肾脏复合终点，定义为肾衰竭、估算肾小球滤过率较基线持续下降≥40%，或因肾脏原因死亡。
结果 本研究共纳入4项文献的合并队列，共计13943例患者。采用Cochrane偏倚风险工具评估纳入研究的质量。分析显示，肾脏复合终点（肾衰竭、估算肾小球滤过率较基线持续下降≥40%，或因肾脏原因死亡）显著降低16%[HR=0.84, 95%CI 0.77~0.92, τ²=0, I²=0%]。非奈利酮还可降低尿白蛋白肌酐比值（SMD=-0.49, 95%CI -0.53~-0.46, τ²<0.0001, I²=0%, 预测区间-0.57~-0.41），并延缓估算肾小球滤过率下降（SMD=-0.32, 95%CI -0.37~-0.27, τ²<0.0001, I²=0%, 预测区间-0.43~-0.21），且未观察到显著异质性。与安慰剂组相比，非奈利酮仅增加高钾血症发生风险（相对风险（relative risk, RR）=2.22, 95%CI 1.93~2.24），其余不良事件发生率无显著差异（RR=1.00, 95%CI 0.98~1.01）。
结论 对于已确诊慢性肾病的2型糖尿病患者，非奈利酮治疗可显著改善肾脏结局，其不良事件谱与安慰剂相当。