Eli Lilly and Company, Indianapolis, IN.
Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada.
Diabetes Care. 2023 Aug 1;46(8):1524-1530. doi: 10.2337/dc23-0231.
Dulaglutide (DU) 1.5 mg was associated with improved composite renal outcomes that included new-onset macroalbuminuria in people with type 2 diabetes with previous cardiovascular disease or cardiovascular risk factors in the REWIND (Researching cardiovascular Events with a Weekly INcretin in Diabetes) trial. This exploratory post hoc analysis evaluated kidney function-related outcomes, excluding the new-onset macroalbuminuria component, among the REWIND participants.
Intent-to-treat analyses were performed on REWIND participants (n = 4,949 DU, n = 4,952 placebo). Time to occurrence of a composite kidney function-related outcome (≥40% sustained decline in estimated glomerular filtration rate [eGFR], per the Chronic Kidney Disease Epidemiology Collaboration 2009 equation, end-stage renal disease, or renal-related death), and mean annual eGFR slope were examined. Analyses were conducted overall and within subgroups defined by baseline urinary albumin-to-creatinine ratio (UACR <30 or ≥30 mg/g) and baseline eGFR (<60 or ≥60 mL/min/1.73 m2).
The post hoc composite kidney function-related outcome occurred less frequently among participants assigned to DU than placebo (hazard ratio [HR] 0.75, 95% CI 0.62-0.92, P = 0.004), with no evidence of a differential DU treatment effect by UACR or eGFR subgroup. A ≥40% sustained eGFR decline occurred less frequently among participants assigned to DU than placebo (HR 0.72, 95% CI 0.58-0.88, P = 0.002). The mean annual decline in eGFR slope was significantly smaller for participants assigned to DU than placebo (-1.37 vs. -1.56 mL/min/1.73 m2/year, P < 0.001); results were similar for all subgroups.
The estimated 25% reduced hazard of a kidney function-related outcome among participants assigned to DU highlights its potential for delaying or slowing the development of diabetic kidney disease in people with type 2 diabetes.
在 REWIND(研究糖尿病每周使用 INCRETIN 治疗心血管事件)试验中,对于患有 2 型糖尿病且伴有心血管疾病或心血管危险因素的患者,与安慰剂相比,度拉鲁肽(DU)1.5mg 可改善复合肾脏结局,包括新发大量白蛋白尿。本探索性事后分析评估了 REWIND 参与者的肾脏功能相关结局,不包括新发大量白蛋白尿成分。
对 REWIND 参与者(n=4949 DU,n=4952 安慰剂)进行意向治疗分析。主要复合肾脏功能相关结局(估计肾小球滤过率[eGFR]持续下降≥40%[根据慢性肾脏病流行病学合作组 2009 方程]、终末期肾病或肾脏相关死亡)的发生时间和平均年度 eGFR 斜率进行了评估。总体和按基线尿白蛋白/肌酐比值(UACR<30 或≥30mg/g)和基线 eGFR(<60 或≥60mL/min/1.73m2)分层进行了分析。
与安慰剂相比,DU 组参与者发生复合肾脏功能相关结局的频率较低(风险比[HR]0.75,95%CI0.62-0.92,P=0.004),且无证据表明 DU 治疗效果存在 UACR 或 eGFR 亚组差异。与安慰剂相比,DU 组参与者发生持续 eGFR 下降≥40%的频率较低(HR0.72,95%CI0.58-0.88,P=0.002)。与安慰剂相比,DU 组参与者的 eGFR 斜率平均每年下降幅度明显较小(-1.37 与-1.56mL/min/1.73m2/年,P<0.001);所有亚组结果均相似。
与安慰剂相比,DU 组参与者发生肾脏功能相关结局的风险降低 25%,这突出表明其在延缓或减缓 2 型糖尿病患者糖尿病肾病的发展方面具有潜力。