Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, Missouri, USA.
Richard L. Roudebush VA Medical Center and Indiana University, Indianapolis, Indiana, USA.
Diabetes Obes Metab. 2023 Jun;25(6):1512-1522. doi: 10.1111/dom.14999. Epub 2023 Feb 26.
To evaluate the effect of finerenone by baseline HbA1c, HbA1c variability, diabetes duration and baseline insulin use on cardiorenal outcomes and diabetes progression.
Composite efficacy outcomes included cardiovascular (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for heart failure), kidney (kidney failure, sustained ≥ 57% estimated glomerular filtration rate decline or renal death) and diabetes progression (new insulin initiation, increase in antidiabetic medication, 1.0% increase in HbA1c from baseline, new diabetic ketoacidosis diagnosis or uncontrolled diabetes).
In 13 026 participants, risk reductions in the cardiovascular and kidney composite outcomes with finerenone versus placebo were consistent across HbA1c quartiles (P interaction .52 and .09, respectively), HbA1c variability (P interaction .48 and .10), diabetes duration (P interaction .12 and .75) and insulin use (P interaction .16 and .52). HbA1c variability in the first year of treatment was associated with a higher risk of cardiovascular and kidney events (hazard ratio [HR] 1.20; 95% confidence interval [CI] 1.07-1.35; P = .0016 and HR 1.36; 95% CI 1.21-1.52; P < .0001, respectively). There was no effect on diabetes progression with finerenone or placebo (HR 1.00; 95% CI 0.95-1.04). Finerenone was well-tolerated across subgroups; discontinuation and hospitalization because of hyperkalaemia were low.
Finerenone efficacy was not modified by baseline HbA1c, HbA1c variability, diabetes duration or baseline insulin use. Greater HbA1c variability appeared to be associated with an increased risk of cardiorenal outcomes.
评估依非尼酮对基线糖化血红蛋白(HbA1c)、HbA1c 变异性、糖尿病病程和基线胰岛素使用对心血管-肾脏结局和糖尿病进展的影响。
复合疗效终点包括心血管(心血管死亡、非致死性心肌梗死、非致死性卒中和心力衰竭住院)、肾脏(肾衰竭、持续估算肾小球滤过率下降≥57%或肾脏死亡)和糖尿病进展(新起始胰岛素、抗糖尿病药物增加、HbA1c 较基线升高 1.0%、新发糖尿病酮症酸中毒诊断或未控制的糖尿病)。
在 13026 名参与者中,与安慰剂相比,依非尼酮降低心血管和肾脏复合结局的风险在 HbA1c 四分位数(交互 P 值分别为.52 和.09)、HbA1c 变异性(交互 P 值分别为.48 和.10)、糖尿病病程(交互 P 值分别为.12 和.75)和胰岛素使用(交互 P 值分别为.16 和.52)上一致。治疗第 1 年的 HbA1c 变异性与心血管和肾脏事件风险升高相关(风险比 [HR] 1.20;95%置信区间 [CI] 1.07-1.35;P =.0016 和 HR 1.36;95% CI 1.21-1.52;P<.0001)。依非尼酮或安慰剂对糖尿病进展均无影响(HR 1.00;95% CI 0.95-1.04)。依非尼酮在各亚组中均耐受良好;高钾血症导致的停药和住院率较低。
依非尼酮的疗效不受基线 HbA1c、HbA1c 变异性、糖尿病病程或基线胰岛素使用的影响。HbA1c 变异性增加似乎与心血管-肾脏结局风险增加相关。