糖尿病联合治疗方案对肾脏血流动力学的影响不同：比较恩格列净/利拉鲁肽与二甲双胍/甘精胰岛素的随机对照临床试验。
Renal hemodynamic effects differ between antidiabetic combination strategies: randomized controlled clinical trial comparing empagliflozin/linagliptin with metformin/insulin glargine.
机构信息
Department of Nephrology and Hypertension, Friedrich-Alexander University Erlangen-Nürnberg, Ulmenweg 18, 91054, Erlangen, Germany.
Department of Nephrology and Hypertension, Paracelsus Medical University, Nuremberg, Germany.
出版信息
Cardiovasc Diabetol. 2021 Sep 4;20(1):178. doi: 10.1186/s12933-021-01358-8.
BACKGROUND
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.
METHODS
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.
RESULTS
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 p < 0.001). Analysis of intraglomerular hemodynamics revealed that E+L did not change resistance of afferent arteriole (R) (p = 0.116), but diminished resistance of efferent arterioles (R) (p = 0.001). In M+I group R was increased (p = 0.006) and R remained unchanged (p = 0.538). The effects on R (p < 0.05) and on R (p < 0.05) differed between the groups.
CONCLUSIONS
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 R and E+L predominantly decreasing R, 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.
背景
2 型糖尿病可引起心肾并发症，并采用不同的联合疗法进行治疗。但这些联合疗法的肾脏血液动力学特征尚未得到详细评估。
方法
97 例 2 型糖尿病患者随机分为恩格列净和利拉鲁肽（E+L 组）或二甲双胍和甘精胰岛素（M+I 组）治疗 3 个月。用对氨马尿酸和菊粉评估肾血浆流量（RPF）和肾小球滤过率（GFR）以评估肾脏血液动力学。根据 Gomez 模型计算肾小球内血液动力学。
结果
E+L 治疗可降低 GFR（p=0.003），但 RPF 保持不变（p=0.536）。相反，M+I 不仅降低 GFR（p=0.001），而且还导致 RPF 显著降低（p<0.001）。E+L 治疗可降低肾血管阻力（RVR）（p=0.001），而 M+I 治疗则增加 RVR（p=0.001）。两组间 RPF 和 RVR 的变化不同（均 p<0.001）。肾小球内血液动力学分析显示，E+L 不改变入球小动脉阻力（R）（p=0.116），但降低出球小动脉阻力（R）（p=0.001）。M+I 组 R 增加（p=0.006），R 保持不变（p=0.538）。两组间 R（p<0.05）和 R（p<0.05）的变化存在差异。
结论
在肾功能正常的 2 型糖尿病患者中，M+I 治疗可导致肾灌注减少和血管阻力增加，而 E+I 治疗可保留肾灌注并降低血管阻力。此外，根据 Gomez 模型估计了对阻力血管的不同潜在作用，M+I 增加 R，E+L 主要降低 R，这与提出的钠-葡萄糖共转运蛋白 2 抑制剂作用相反。
试验注册
该研究于 2016 年 4 月 26 日在 www.clinicaltrials.gov（NCT02752113）注册。
Zotero 插件