Department of Internal Medicine, Diabetes Center, VU University Medical Center, Amsterdam, The Netherlands.
Department of Health Sciences and the EMGO Institute for Health and Care Research, VU University Amsterdam, Amsterdam, The Netherlands.
Diabetes Obes Metab. 2017 Dec;19(12):1669-1680. doi: 10.1111/dom.12985. Epub 2017 Jul 25.
To determine whether lixisenatide, a prandial short-acting glucagon-like peptide receptor agonist (GLP-1RA), ameliorates postprandial glomerular hyperfiltration in patients with type 2 diabetes mellitus (T2DM) compared with insulin-glulisine (iGlu).
Postprandial renal haemodynamic effects of 8-week treatment with lixisenatide 20 µg vs once-daily titrated iGlu were measured in 35 overweight patients with T2DM inadequately controlled on insulin-glargine, with or without metformin [mean ± SD age 62 ± 7 years, HbA1c 8.0% ± 0.9%, estimated glomerular filtration rate (GFR) 85 ± 12 mL/min/1.73 m , median (IQR) urinary albumin/creatinine ratio 1.5 (0.9-3.0) mg/mmol]. After a standardised breakfast, GFR (primary endpoint) and effective renal plasma flow (ERPF) were determined by inulin and para-aminohippuric acid renal clearance, respectively, based on timed urine sampling. Intrarenal haemodynamic functions were estimated using Gomez equations.
Compared with iGlu, lixisenatide did not affect GFR [+0.1 mL/min/1.73 m (95% CI -9 to 9)], ERPF [-17 mL/min/1.73 m (-61 to 26)], other (intra-)renal haemodynamics or renal damage markers, but increased fractional sodium excretion [+0.25% (0.09-0.41)] and urinary pH [+0.7 (0.3-1.2)]. Plasma renin, angiotensin-II and aldosterone were unchanged. Lixisenatide and iGlu reduced HbA1c similarly, by 0.8% ± 0.1% and 0.6% ± 0.1%, respectively, while postprandial glucose was lower with lixisenatide (P = .002). Compared with iGlu, lixisenatide reduced bodyweight [-1.4 kg (-2.5 to -0.2)] and increased postprandial mean arterial pressure [+9 mm Hg (4-14)].
Eight-week lixisenatide treatment does not affect postprandial (intra-)renal haemodynamics compared with iGlu when added to insulin-glargine in patients with T2DM without overt nephropathy. Prolonged lixisenatide treatment has a sustained natriuretic effect, which is in contrast to previous reports on long-acting GLP-1RA, reduces body weight and increases postprandial blood pressure compared with iGlu.
ClinicalTrials.gov identifier NCT02276196.
比较利西拉肽与胰岛素-谷赖胰岛素（iGlu）治疗 8 周后，2 型糖尿病（T2DM）患者餐后肾小球高滤过的改善情况，利西拉肽是一种短效胰高血糖素样肽受体激动剂（GLP-1RA）。
35 例超重 T2DM 患者在胰岛素-甘精胰岛素治疗的基础上，加用或不加二甲双胍，血糖控制不佳，用利西拉肽 20 µg 或每日滴定 iGlu 治疗 8 周，测量餐后肾血流动力学效应[平均（±SD）年龄 62（±7）岁，糖化血红蛋白（HbA1c）8.0%（±0.9%），估计肾小球滤过率（GFR）85（±12）mL/min/1.73 m ，中位数（IQR）尿白蛋白/肌酐比值 1.5（0.9-3.0）mg/mmol]。口服标准早餐后，通过菊粉和对氨基马尿酸盐肾清除率分别测定肾小球滤过率（主要终点）和有效肾血浆流量（ERPF），并根据定时尿液取样。使用 Gomez 方程估计肾内血流动力学功能。
与 iGlu 相比，利西拉肽对 GFR[+0.1 mL/min/1.73 m（95%CI-9 至 9）]、ERPF[-17 mL/min/1.73 m（-61 至 26）]、其他（肾内）血流动力学或肾损伤标志物无影响，但增加了钠排泄分数[+0.25%（0.09-0.41）]和尿 pH 值[+0.7（0.3-1.2）]。血浆肾素、血管紧张素-II 和醛固酮无变化。利西拉肽和 iGlu 分别使 HbA1c 降低 0.8%（±0.1%）和 0.6%（±0.1%），而餐后血糖水平利西拉肽组更低（P=0.002）。与 iGlu 相比，利西拉肽降低体重[-1.4 kg（-2.5 至-0.2）]，并增加餐后平均动脉压[+9 mm Hg（4-14）]。
在无明显肾病的 T2DM 患者中，与胰岛素-甘精胰岛素联合应用时，与 iGlu 相比，利西拉肽治疗 8 周不会影响餐后（肾内）血流动力学。与之前关于长效 GLP-1RA 的报告相反，利西拉肽的长期治疗具有持续的利钠作用，与 iGlu 相比，它还降低体重并增加餐后血压。
ClinicalTrials.gov 标识符 NCT02276196。
