Type 2 diabetes causes cardio-renal complications and is treated with different combination therapies. The renal hemodynamics profile of such combination therapies has not been evaluated in detail. Patients (N = 97) with type 2 diabetes were randomized to receive either empagliflozin and linagliptin (E+L group) or metformin and insulin glargine (M+I group) for 3 months. Renal hemodynamics were assessed with para-aminohippuric acid and inulin for renal plasma flow (RPF) and glomerular filtration rate (GFR). Intraglomerular hemodynamics were calculated according the Gomez´ model. Treatment with E+L reduced GFR (p = 0.003), but RPF remained unchanged (p = 0.536). In contrast, M+I not only reduced GFR (p = 0.001), but also resulted in a significant reduction of RPF (p < 0.001). Renal vascular resistance (RVR) decreased with E+L treatment (p = 0.001) but increased with M+I treatment (p = 0.001). The changes in RPF and RVR were different between the two groups (both padjust < 0.001). Analysis of intraglomerular hemodynamics revealed that E+L did not change resistance of afferent arteriole (RA) (p = 0.116), but diminished resistance of efferent arterioles (RE) (p = 0.001). In M+I group RA was increased (p = 0.006) and RE remained unchanged (p = 0.538). The effects on RA (padjust < 0.05) and on RE (padjust < 0.05) differed between the groups. In patients with type 2 diabetes and preserved renal function treatment with M+I resulted in reduction of renal perfusion and increase in vascular resistance, in contrast to treatment with E+I that preserved renal perfusion and reduced vascular resistance. Moreover, different underlying effects on the resistance vessels have been estimated according to the Gomez model, with M+I increasing RA and E+L predominantly decreasing RE, which is in contrast to the proposed sodium-glucose cotransporter 2 inhibitor effects. Trial registration: The study was registered at www.clinicaltrials.gov (NCT02752113) on April 26, 2016

中文翻译：

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抗糖尿病联合策略之间的肾脏血流动力学效应不同：比较恩格列净/利格列汀与二甲双胍/甘精胰岛素的随机对照临床试验

2 型糖尿病会导致心肾并发症，并采用不同的联合疗法进行治疗。尚未详细评估此类联合疗法的肾脏血流动力学特征。2 型糖尿病患者 (N = 97) 随机接受 empagliflozin 和 linagliptin（E+L 组）或二甲双胍和甘精胰岛素（M+I 组）治疗 3 个月。用对氨基马尿酸和菊粉评估肾血流动力学的肾血浆流量 (RPF) 和肾小球滤过率 (GFR)。根据 Gomez 模型计算肾小球内血流动力学。E+L 治疗降低了 GFR (p = 0.003)，但 RPF 保持不变 (p = 0.536)。相比之下，M+I 不仅降低了 GFR (p = 0.001)，而且还导致 RPF 显着降低 (p < 0.001)。E+L 治疗后肾血管阻力 (RVR) 降低 (p = 0. 001) 但随着 M+I 处理而增加 (p = 0.001)。两组之间 RPF 和 RVR 的变化不同（均 padjust < 0.001）。肾小球内血流动力学分析显示，E+L 不会改变传入小动脉 (RA) 的阻力 (p = 0.116)，但会降低传出小动脉 (RE) 的阻力 (p = 0.001)。在 M+I 组中，RA 增加（p = 0.006），RE 保持不变（p = 0.538）。组间对 RA (padjust < 0.05) 和 RE (padjust < 0.05) 的影响不同。在保留肾功能的 2 型糖尿病患者中，用 M+I 治疗导致肾灌注减少和血管阻力增加，与用 E+I 治疗保持肾灌注和降低血管阻力形成对比。而且，根据 Gomez 模型估计了对阻力血管的不同潜在影响，其中 M+I 增加 RA，E+L 主要降低 RE，这与提出的钠-葡萄糖协同转运蛋白 2 抑制剂的作用形成对比。试验注册：该研究于 2016 年 4 月 26 日在 www.clinicaltrials.gov (NCT02752113) 注册