Linagliptin and its effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction: the randomized MARLINA-T2D trial.
Linagliptin and its effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction: the randomized MARLINA-T2D trial.
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DOI：
10.1111/dom.13041
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发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
von Eynatten M
中科院分区：
文献类型：
--
作者：
Groop PH;Cooper ME;Perkovic V;Hocher B;Kanasaki K;Haneda M;Schernthaner G;Sharma K;Stanton RC;Toto R;Cescutti J;Gordat M;Meinicke T;Koitka-Weber A;Thiemann S;von Eynatten M
MARLINA‐T2D 研究（ClinicalTrials.gov，NCT01792518）旨在研究利格列汀添加到标准护理中对 2 型糖尿病和蛋白尿患者的血糖和肾脏影响。总共 360 名 2 型糖尿病患者，尽管使用单一药物，HbA1c 为 6.5% 至 10.0% (48–86 mmol/mol)，估计肾小球滤过率 (eGFR) ≥30 mL/min/1.73 m2，尿白蛋白肌酐比 (UACR) 30–3000 mg/g肾素-血管紧张素-系统阻断被随机分为双盲组 利格列汀 (n = 182) 或安慰剂 (n = 178) 24 周。主要和关键次要终点分别是第 24 周时 HbA1c 相对于基线的变化以及 24 周内 UACR 相对于基线的百分比变化的时间加权平均值。基线平均 HbA1c 和几何平均 (gMean) UACR 分别为 7.8%±0.9% (62.2±9.6mmol/mol) 和 126mg/g； 73.7% 和 20.3% 的参与者分别患有微量白蛋白尿或大量白蛋白尿。 24 周后，安慰剂调整后的 HbA1c 相对于基线的平均变化为 -0.60% (-6.6 mmol/mol)（95% 置信区间 [CI]，-0.78 至 -0.43 [-8.5 至 -4.7 mmol/mol]；P < .0001）。 UACR 相对于基线的时间加权百分比变化的安慰剂调整 gMean 为 -6.0%（95% CI，-15.0 至 3.0；P = .1954）。利格列汀组和安慰剂组的不良事件概况（包括肾脏安全性和 eGFR 变化）相似。在糖尿病肾病早期阶段的个体中，利格列汀显着改善血糖控制，但没有显着降低蛋白尿。安慰剂调整后的 eGFR 没有显着变化。检测利格列汀的临床相关肾脏影响可能需要更长时间的治疗，因为其在动物研究中的主要实验效果是减少间质纤维化而不是改变肾小球血流动力学。
The MARLINA‐T2D study (ClinicalTrials.gov, NCT01792518) was designed to investigate the glycaemic and renal effects of linagliptin added to standard‐of‐care in individuals with type 2 diabetes and albuminuria. A total of 360 individuals with type 2 diabetes, HbA1c 6.5% to 10.0% (48–86 mmol/mol), estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 and urinary albumin‐to‐creatinine ratio (UACR) 30–3000 mg/g despite single agent renin‐angiotensin‐system blockade were randomized to double‐blind linagliptin (n = 182) or placebo (n = 178) for 24 weeks. The primary and key secondary endpoints were change from baseline in HbA1c at week 24 and time‐weighted average of percentage change from baseline in UACR over 24 weeks, respectively. Baseline mean HbA1c and geometric mean (gMean) UACR were 7.8% ± 0.9% (62.2 ± 9.6 mmol/mol) and 126 mg/g, respectively; 73.7% and 20.3% of participants had microalbuminuria or macroalbuminuria, respectively. After 24 weeks, the placebo‐adjusted mean change in HbA1c from baseline was −0.60% (−6.6 mmol/mol) (95% confidence interval [CI], −0.78 to −0.43 [−8.5 to −4.7 mmol/mol]; P < .0001). The placebo‐adjusted gMean for time‐weighted average of percentage change in UACR from baseline was −6.0% (95% CI, −15.0 to 3.0; P = .1954). The adverse‐event profile, including renal safety and change in eGFR, was similar between the linagliptin and placebo groups. In individuals at early stages of diabetic kidney disease, linagliptin significantly improved glycaemic control but did not significantly lower albuminuria. There was no significant change in placebo‐adjusted eGFR. Detection of clinically relevant renal effects of linagliptin may require longer treatment, as its main experimental effects in animal studies have been to reduce interstitial fibrosis rather than alter glomerular haemodynamics.
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DOI：
10.1111/dom.12832
发表时间：
2017-03
期刊：
Diabetes, obesity & metabolism
影响因子：
--
作者：
Goldenberg R;Gantz I;Andryuk PJ;O'Neill EA;Kaufman KD;Lai E;Wang YN;Suryawanshi S;Engel SS
通讯作者：
Engel SS
影响因子：
2
作者：
MIETTINEN, O;NURMINEN, M
通讯作者：
NURMINEN, M
影响因子：
3.5
作者：
Donnan, PT;MacDonald, TM;Morris, AD
通讯作者：
Morris, AD
影响因子：
16.2
作者：
Kirkman MS;Rowan-Martin MT;Levin R;Fonseca VA;Schmittdiel JA;Herman WH;Aubert RE
通讯作者：
Aubert RE
影响因子：
3.8
作者：
Hauber, A. Brett;Tunceli, Kaan;Radican, Larry
通讯作者：
Radican, Larry