Providence Health Care, University of Washington, Spokane, Washington.
Division of Nephrology and Hypertension, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa.
Kidney360. 2020 Dec 8;2(2):254-262. doi: 10.34067/KID.0005852020. eCollection 2021 Feb 25.
In the AWARD-7 trial of participants with type 2 diabetes (T2DM) and moderate-to-severe CKD, dulaglutide (DU) treatment slowed decline in eGFR compared with insulin glargine (IG). Treatment with doses of either DU or IG resulted in similar levels of glycemic control and BP. The aim of this analysis was to determine the risk of clinical event outcomes between treatment groups.
Participants with T2DM and CKD categories 3-4 were randomized (1:1:1) to 0.75 or 1.5 mg DU weekly or IG daily as basal therapy, with titrated insulin lispro, for 1 year. The time to occurrence of the composite outcome of ≥40% eGFR decline, ESKD, or death due to kidney disease was compared using a Cox proportional-hazards model.
Patients treated with 1.5 mg DU weekly versus IG daily for 1 year had a lower risk of ≥40% eGFR decline or ESKD events in the overall study population (5% versus 11%; hazard ratio, 0.45; 95% CI, 0.20 to 0.97; =0.04). Most events occurred in the subset of patients with macroalbuminuria, where risk of the composite outcome was substantially lower for 1.5 mg DU versus IG (7% versus 22%; hazard ratio, 0.25; 95% CI, 0.10 to 0.68; =0.006). No deaths due to kidney disease occurred.
Treatment with 1.5 mg DU weekly was associated with a clinically relevant risk reduction of ≥40% eGFR decline or ESKD compared with IG daily, particularly in the macroalbuminuria subgroup of participants with T2DM and moderate-to-severe CKD.
在 AWARD-7 试验中，纳入了 2 型糖尿病（T2DM）且合并中重度 CKD 的患者，与甘精胰岛素（IG）相比，度拉糖肽（DU）治疗可减缓 eGFR 的下降速度。DU 或 IG 的治疗剂量可使血糖控制和血压达到相似水平。本分析旨在比较不同治疗组间临床事件结局的风险。
将 T2DM 合并 CKD 3-4 期患者按 1:1:1 随机分为三组，分别接受每周 0.75 或 1.5mgDU 或每日一次 IG 作为基础治疗，同时给予胰岛素赖脯肽滴定治疗，持续 1 年。采用 Cox 比例风险模型比较发生 eGFR 下降≥40%、ESKD 或因肾脏疾病死亡的复合结局的时间。
在整个研究人群中，与每日一次 IG 相比，接受每周 1.5mgDU 治疗的患者在 1 年内发生 eGFR 下降≥40%或 ESKD 事件的风险较低（5% vs. 11%；风险比，0.45；95%CI，0.20 至 0.97；=0.04）。大多数事件发生在白蛋白尿亚组中，与 IG 相比，1.5mgDU 治疗的复合结局风险显著降低（7% vs. 22%；风险比，0.25；95%CI，0.10 至 0.68；=0.006）。无因肾脏疾病导致的死亡。
与每日一次 IG 相比，每周 1.5mgDU 治疗可显著降低 eGFR 下降≥40%或 ESKD 的风险，特别是在合并中重度 CKD 的 T2DM 患者中白蛋白尿亚组。
