Department of Diabetes Complications Research, Steno Diabetes Center, Gentofte, Denmark.
Department of Clinical Physiology & Nuclear Medicine & PET, Rigshospitalet, Glostrup Hospital, Glostrup, Denmark.
Diabetes Obes Metab. 2017 Feb;19(2):239-247. doi: 10.1111/dom.12808. Epub 2016 Nov 21.
Among patients with type 2 diabetes and albuminuria, cardiorenal morbidity and mortality are high despite multifactorial treatment. Short-term reduction in albuminuria is considered suggestive of long-term renoprotective effects. We evaluated the renal effects of the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide on top of multifactorial care, including renin-angiotensin-system (RAS)-inhibition.
Randomized, double-blind, placebo-controlled, cross-over trial including patients with type 2 diabetes and persistent albuminuria (urinary albumin-to-creatinine ratio >30 mg/g) and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m . Patients received liraglutide (1.8 mg/d) and matched placebo for 12 weeks in a random order. The primary endpoint was change in 24-h urinary albumin excretion rate (UAER).
A total of 32 patients were randomized and 27 completed the study. After placebo treatment, geometric mean (IQR) UAER was 199 (81-531) mg/24-h, mean (SD) measured GFR (mGFR) 75 (36) mL/min/1.73 m , 24-h blood pressure 145/80 (15/8) mm Hg and HbA1c 61 (11) mmol/mol. Liraglutide reduced HbA1c by 8 (95% CI: 5; 11) mmol/mol (P < .001) and weight by 1.8 (95% CI: 0.2; 3.4) kg (P = .032) compared to placebo. Furthermore, liraglutide reduced UAER by 32 (95% CI: 7; 50)% ( P = .017) compared with placebo. The change in mGFR was -5 (95% CI: -11; 2) mL/min/1.73 m ( P = .15), and change in 24-h systolic blood pressure was -5 (95% CI: -10; 0) mm Hg ( P = .07). In multivariate regression models, change in UAER was associated with change in 24-h systolic blood pressure ( P = .025) but not with change in HbA1c, weight or mGFR ( P ≥ .14), overall model R = .39.
Our placebo-controlled randomized trial suggests that liraglutide has renoprotective effects on top of multifactorial treatment, including RAS-inhibition, in patients with type 2 diabetes and albuminuria.
在患有 2 型糖尿病和白蛋白尿的患者中，尽管进行了多因素治疗，但心肾发病率和死亡率仍然很高。白蛋白尿的短期减少被认为提示长期的肾脏保护作用。我们评估了胰高血糖素样肽-1（GLP-1）受体激动剂利拉鲁肽在多因素治疗（包括肾素-血管紧张素系统（RAS）抑制）基础上对肾脏的影响。
这是一项随机、双盲、安慰剂对照、交叉试验，纳入了患有 2 型糖尿病和持续白蛋白尿（尿白蛋白与肌酐比值>30mg/g）和估计肾小球滤过率（eGFR）≥30mL/min/1.73m 的患者。患者随机接受利拉鲁肽（1.8mg/d）和匹配的安慰剂治疗 12 周。主要终点是 24 小时尿白蛋白排泄率（UAER）的变化。
共有 32 名患者被随机分组，27 名患者完成了研究。在安慰剂治疗后，几何均数（IQR）UAER 为 199（81-531）mg/24-h，平均（SD）测量肾小球滤过率（mGFR）为 75（36）mL/min/1.73m ，24 小时血压为 145/80（15/8）mmHg，糖化血红蛋白（HbA1c）为 61（11）mmol/mol。与安慰剂相比，利拉鲁肽可使 HbA1c 降低 8（95%CI：5；11）mmol/mol（P<0.001），体重降低 1.8（95%CI：0.2；3.4）kg（P=0.032）。此外，与安慰剂相比，利拉鲁肽可使 UAER 降低 32（95%CI：7；50）%（P=0.017）。mGFR 的变化为-5（95%CI：-11；2）mL/min/1.73m（P=0.15），24 小时收缩压的变化为-5（95%CI：-10；0）mmHg（P=0.07）。在多变量回归模型中，UAER 的变化与 24 小时收缩压的变化相关（P=0.025），但与 HbA1c、体重或 mGFR 的变化无关（P≥0.14），总体模型 R=0.39。
我们的安慰剂对照随机试验表明，在多因素治疗（包括 RAS 抑制）的基础上，利拉鲁肽对 2 型糖尿病合并白蛋白尿患者具有肾脏保护作用。
