Zobel Emilie Hein, von Scholten Bernt Johan, Lindhardt Morten, Persson Frederik, Hansen Tine Willum, Rossing Peter
Steno Diabetes Center, Gentofte, Denmark.
Steno Diabetes Center, Gentofte, Denmark.
J Diabetes Complications. 2017 Jan;31(1):162-168. doi: 10.1016/j.jdiacomp.2016.09.016. Epub 2016 Sep 30.
AIMS/HYPOTHESIS: Management of diabetic nephropathy includes reduction of albuminuria, blood pressure and weight. The GLP-1 receptor agonist liraglutide may possess these pleiotropic effects in addition to the glucose lowering effect. We aimed to elucidate the individual liraglutide treatment response by determining if high responders (highest reduction) in each risk factor also had high response in other renal risk factors (cross-dependency).
Open-label study: 31 type 2 diabetics treated with liraglutide for 7weeks. After 3weeks washout 23 re-started treatment and were followed for 1year. HbA, weight, systolic blood pressure (SBP), urinary albumin excretion rate (UAER) and mGFR (Cr-EDTA) were evaluated. Changes in high (Q4) vs. low responders (Q1-Q3) were compared for each renal risk factor. The effects of treatment/off treatment/re-treatment (off-on/off-on effect) were evaluated to account for random effects.
After 7weeks HbA was reduced 6(95% CI: 3;9)mmol/mol, weight 2.5(1.8;3.2)kg, SBP 4(-1;9)mmHg, UAER 30(12;44)% and mGFR 11(7;14)ml/min per 1.73m. mGFR high responders had a significant reduction in weight compared to low responders (4.3 vs. 1.9kg; p=0.002). SBP high responders had a tendency of a higher reduction in UAER compared to low responders (47 vs. 23%, p=0.14). No cross-dependency was observed in any of the other renal risk factors (p≥0.16). Treatment response did not differ after 7weeks and 1year (p≥0.12).
CONCLUSIONS/INTERPRETATION: Liraglutide possesses pleiotropic effects on renal risk factors. On patient level, effect on the individual risk factor cannot be anticipated based on response in other risk factors. Response when re-starting treatment did not differ, indicating that our primary findings were not random.
目的/假设：糖尿病肾病的管理包括降低蛋白尿、血压和体重。胰高血糖素样肽-1（GLP-1）受体激动剂利拉鲁肽除具有降糖作用外，可能还具有这些多效性作用。我们旨在通过确定每个危险因素中的高反应者（降低幅度最大）在其他肾脏危险因素中是否也有高反应（交叉依赖性）来阐明利拉鲁肽的个体治疗反应。
开放标签研究：31例2型糖尿病患者接受利拉鲁肽治疗7周。经过3周的洗脱期后，23例患者重新开始治疗并随访1年。评估糖化血红蛋白（HbA）、体重、收缩压（SBP）、尿白蛋白排泄率（UAER）和肾小球滤过率（mGFR，采用铬-乙二胺四乙酸法）。比较每个肾脏危险因素中高反应者（第4四分位数）与低反应者（第1 - 3四分位数）的变化。评估治疗/停药/再治疗的效果（停药-用药/停药-用药效应）以考虑随机效应。
7周后，糖化血红蛋白降低6（95%置信区间：3；9）mmol/mol，体重降低2.5（1.8；3.2）kg，收缩压降低4（-1；9）mmHg，尿白蛋白排泄率降低30（12；44）%，每1.73平方米的肾小球滤过率增加11（7；14）ml/分钟。与低反应者相比，肾小球滤过率高反应者的体重显著降低（4.3对1.9kg；p = 0.002）。与低反应者相比，收缩压高反应者的尿白蛋白排泄率降低趋势更高（47%对23%，p = 0.14）。在任何其他肾脏危险因素中均未观察到交叉依赖性（p≥0.16）。7周和1年后的治疗反应无差异（p≥0.12）。
结论/解读：利拉鲁肽对肾脏危险因素具有多效性作用。在患者层面，无法根据其他危险因素的反应来预测对个体危险因素的影响。重新开始治疗时的反应无差异，表明我们的主要发现并非随机现象。
