Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, Location VUMC, Amsterdam, The Netherlands.
Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Dusseldorf, Germany.
Diabetes Obes Metab. 2022 Jan;24(1):115-124. doi: 10.1111/dom.14557. Epub 2021 Oct 6.
To determine the effect of the dipeptidyl peptidase-4 inhibitor linagliptin on postprandial glomerular hyperfiltration compared with the sulphonylurea glimepiride in adults with type 2 diabetes (T2D).
In this predefined substudy within a randomized, double-blind, parallel-group, intervention trial, overweight people with T2D without renal impairment were treated with once-daily linagliptin 5 mg (N = 10) or glimepiride 1 mg (N = 13) as an add-on to metformin for 8 weeks. After a standardized liquid protein-rich meal, the glomerular filtration rate (GFR) and effective renal plasma flow were determined by inulin and para-aminohippuric acid clearance, respectively, based on timed urine sampling. Intrarenal haemodynamics were estimated using the Gomez equations. Glucoregulatory/vasoactive hormones, urinary pH and fractional excretions (FE) of sodium, potassium and urea were measured.
Compared with glimepiride, linagliptin increased the postprandial filtration fraction (FF; mean difference 2.1%-point; P = .016) and estimated glomerular hydraulic pressure (mean difference 3.0 mmHg; P = .050), and tended to increase GFR (P = .08) and estimated efferent renal arteriolar resistance (R ; P = .08) from baseline to week 8. No differences in FE were noted. Glimepiride reduced HbA1c more than linagliptin (mean difference -0.40%; P = .004), without between-group differences in time-averaged postprandial glucose levels. In the linagliptin group, change in FF correlated with change in mean arterial pressure (R = 0.807; P = .009) and time-averaged mean glucagon (R = 0.782; P = .008), but not with changes in glucose, insulin, intact glucagon-like peptide-1, renin or FE . Change in glucagon was associated with change in R (R = 0.830; P = .003).
In contrast to our hypothesis, compared with glimepiride, linagliptin does not reduce postprandial hyperfiltration, yet appears to increase FF after meal ingestion by increasing blood pressure or R .
在患有 2 型糖尿病（T2D）的成年人中，与磺酰脲类格列美脲相比，二肽基肽酶-4 抑制剂利拉利汀对餐后肾小球高滤过的影响。
在这项随机、双盲、平行组、干预试验的预先设定的亚研究中，无肾功能损害的超重 T2D 患者接受每日一次利拉利汀 5mg（N=10）或格列美脲 1mg（N=13）作为二甲双胍的附加治疗，持续 8 周。在标准化的富含液体蛋白的餐后，通过定时尿液采样，分别使用菊粉和对氨基马尿酸清除率来确定肾小球滤过率（GFR）和有效肾血浆流量。使用 Gomez 方程估计肾内血液动力学。测量葡萄糖调节/血管活性激素、尿 pH 值以及钠、钾和尿素的分数排泄率（FE）。
与格列美脲相比，利拉利汀增加了餐后滤过分数（FF；平均差异 2.1%；P=0.016）和估计的肾小球液压（平均差异 3.0mmHg；P=0.050），并趋于增加 GFR（P=0.08）和估计的出球肾小动脉阻力（R；P=0.08）从基线到第 8 周。FE 没有差异。格列美脲降低 HbA1c 的效果优于利拉利汀（平均差异-0.40%；P=0.004），但餐后血糖水平的时间平均值在两组间无差异。在利拉利汀组，FF 的变化与平均动脉压的变化相关（R=0.807；P=0.009）和平均胰高血糖素时间（R=0.782；P=0.008），但与葡萄糖、胰岛素、完整胰高血糖素样肽-1、肾素或 FE 的变化无关。胰高血糖素的变化与 R 的变化相关（R=0.830；P=0.003）。
与我们的假设相反，与格列美脲相比，利拉利汀不会减少餐后高滤过，但似乎通过增加血压或 R 来增加餐后 FF。
