Linagliptin lowers albuminuria on top of recommended standard treatment in patients with type 2 diabetes and renal dysfunction.
Linagliptin lowers albuminuria on top of recommended standard treatment in patients with type 2 diabetes and renal dysfunction.
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DOI：
10.2337/dc13-0323
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发表时间：
2013-11
期刊：
影响因子：
16.2
通讯作者：
von Eynatten M
中科院分区：
文献类型：
--
作者：
Groop PH;Cooper ME;Perkovic V;Emser A;Woerle HJ;von Eynatten M
临床前数据表明，利格列汀（一种二肽基肽酶 4 抑制剂）可能会降低尿白蛋白排泄。通过汇总四项类似设计的 24 周、随机、双盲、安慰剂对照 III 期试验的数据，分析了利格列汀在抑制人类肾素-血管紧张素-醛固酮系统 (RAAS) 的基础上降低白蛋白尿的能力。对四项已完成研究的汇总分析确定了 217 名受试者患有 2 型糖尿病和普遍存在白蛋白尿（定义为尿白蛋白与肌酐比值 [UACR] 为 30−3,000 mg/g 肌酐），同时接受稳定剂量的 RAAS 抑制剂。参与者被随机分配服用利格列汀 5 毫克/天 (n = 162) 或安慰剂 (n = 55)。主要终点是 UACR 几何平均数从基线到第 24 周的百分比变化。利格列汀组在第 24 周时的 UACR 降低了 32%（95% CI -42 至 -21；P < 0.05），而安慰剂组为 6%（95% CI -27 至 +23），组间差异为 28%（95% CI -47 至 -2；P = 0.0357）。从基线到第 24 周，HbA1c 变化的组间差异为 -0.61% (-6.7 mmol/mol)，有利于利格列汀 (95% CI -0.88 至 -0.34% [-9.6 至 -3.7 mmol/mol]；P < 0.0001)。然而，利格列汀降低蛋白尿的作用不受种族或基线或治疗后 HbA1c 和收缩压 (SBP) 值的影响。利格列汀与稳定的 RAAS 抑制剂联合使用可使 2 型糖尿病和肾功能不全患者的蛋白尿显着减少。该观察结果与葡萄糖水平或收缩压的变化无关。进一步研究利格列汀对肾脏的影响的前瞻性研究正在进行中。
Preclinical data suggest that linagliptin, a dipeptidyl peptidase-4 inhibitor, may lower urinary albumin excretion. The ability of linagliptin to lower albuminuria on top of renin-angiotensin-aldosterone system (RAAS) inhibition in humans was analyzed by pooling data from four similarly designed, 24-week, randomized, double-blind, placebo-controlled, phase III trials. A pooled analysis of four completed studies identified 217 subjects with type 2 diabetes and prevalent albuminuria (defined as a urinary albumin-to-creatinine ratio [UACR] of 30−3,000 mg/g creatinine) while receiving stable doses of RAAS inhibitors. Participants were randomized to either linagliptin 5 mg/day (n = 162) or placebo (n= 55). The primary end point was the percentage change in geometric mean UACR from baseline to week 24. UACR at week 24 was reduced by 32% (95% CI −42 to −21; P < 0.05) with linagliptin compared with 6% (95% CI −27 to +23) with placebo, with a between-group difference of 28% (95% CI −47 to −2; P = 0.0357). The between-group difference in the change in HbA1c from baseline to week 24 was −0.61% (−6.7 mmol/mol) in favor of linagliptin (95% CI −0.88 to −0.34% [−9.6 to −3.7 mmol/mol]; P < 0.0001). The albuminuria-lowering effect of linagliptin, however, was not influenced by race or HbA1c and systolic blood pressure (SBP) values at baseline or after treatment. Linagliptin administered in addition to stable RAAS inhibitors led to a significant reduction in albuminuria in patients with type 2 diabetes and renal dysfunction. This observation was independent of changes in glucose level or SBP. Further research to prospectively investigate the renal effects of linagliptin is underway.
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影响因子：
16.2
作者：
Molitch ME;Steffes M;Sun W;Rutledge B;Cleary P;de Boer IH;Zinman B;Lachin J;Epidemiology of Diabetes Interventions and Complications Study Group
通讯作者：
Epidemiology of Diabetes Interventions and Complications Study Group
影响因子：
168.9
作者：
Matsushita, Kunihiro;van der Velde, Marije;Astor, Brad C.;Woodward, Mark;Levey, Andrew S.;de Jong, Paul E.;Coresh, Josef;Gansevoort, Ron T.
通讯作者：
Gansevoort, Ron T.
DOI：
10.1124/jpet.111.186866
发表时间：
2012-02-01
影响因子：
3.5
作者：
Liu, Wei Jing;Xie, Shu Hua;Park, Tae Sun
通讯作者：
Park, Tae Sun
影响因子：
5.8
作者：
Del Prato, S.;Barnett, A. H.;Dugi, K. A.
通讯作者：
Dugi, K. A.
影响因子：
5.8
作者：
Haak, T.;Meinicke, T.;Woerle, H. -J.
通讯作者：
Woerle, H. -J.