Korakas Emmanouil, Thymis John, Oikonomou Evangelos, Mourouzis Konstantinos, Kountouri Aikaterini, Pliouta Loukia, Pililis Sotirios, Pavlidis George, Lampsas Stamatios, Katogiannis Konstantinos, Palaiodimou Lina, Tsivgoulis Georgios, Siasos Gerasimos, Ikonomidis Ignatios, Raptis Athanasios, Lambadiari Vaia
2nd Department of Internal Medicine Research Unit and Diabetes Centre, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Rimini 1 Str., Chaidari, 12462 Athens, Greece.
2nd Department of Cardiology Laboratory of Preventive Cardiology and Echocardiography Department, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece.
J Clin Med. 2024 Dec 10;13(24):7497. doi: 10.3390/jcm13247497.
: The association between diabetic nephropathy and arterial elasticity and endothelial function is well established. In this study, we compared the effect of the combination of dulaglutide and dapagliflozin versus DPP-4 inhibitors on the endothelial glycocalyx, arterial stiffness, myocardial function, and albuminuria. : Overall, 60 patients were randomized to combined dulaglutide and dapagliflozin treatment (n = 30) or DPP-4 inhibitors (DPP-4i, n = 30) (ClinicalTrials.gov: NCT06611904). We measured at baseline and 4 and 12 months post-treatment: (i) the perfused boundary region of the sublingual arterial microvessels, (ii) pulse wave velocity (PWV) and central systolic blood pressure (cSBP), (iii) global left ventricular longitudinal strain (GLS), and (iv) urine albumin-to-creatinine ratio (UACR). : After twelve months, dual therapy showed greater improvements vs. DPP-4i in PBR (2.10 ± 0.31 to 1.93 ± 0.23 μm vs. 2.11 ± 0.31 to 2.08 ± 0.28 μm, < 0.001), UACR (326 ± 61 to 142 ± 47 mg/g vs. 345 ± 48 to 306 ± 60 mg/g, < 0.01), and PWV (11.77 ± 2.37 to 10.7 ± 2.29 m/s vs. 10.64 ± 2.44 to 10.54 ± 2.84 m/s, < 0.001), while only dual therapy showed improvement in cSBP (130.21 ± 17.23 to 123.36 ± 18.42 mmHg). These effects were independent of glycemic control. Both treatments improved GLS, but the effect of dual therapy was significantly higher compared to DPP-4i (18.19% vs. 6.01%, respectively). : Twelve-month treatment with dulaglutide and dapagliflozin showed a greater improvement in arterial stiffness, endothelial function, myocardial function, and albuminuria than DPP-4is. Early initiation of combined therapy as an add-on to metformin should be considered in these patients.
糖尿病肾病与动脉弹性和内皮功能之间的关联已得到充分证实。在本研究中，我们比较了度拉糖肽和达格列净联合用药与二肽基肽酶-4（DPP-4）抑制剂对内皮糖萼、动脉僵硬度、心肌功能和蛋白尿的影响。总体而言，60例患者被随机分为度拉糖肽和达格列净联合治疗组（n = 30）或DPP-4抑制剂组（DPP-4i，n = 30）（ClinicalTrials.gov：NCT06611904）。我们在基线以及治疗后4个月和12个月测量了：（i）舌下动脉微血管的灌注边界区域，（ii）脉搏波速度（PWV）和中心收缩压（cSBP），（iii）整体左心室纵向应变（GLS），以及（iv）尿白蛋白与肌酐比值（UACR）。十二个月后，与DPP-4i相比，联合治疗在灌注边界区域（PBR）（从2.10±0.31μm改善至1.93±0.23μm，而DPP-4i组从2.11±0.31μm改善至2.08±0.28μm，P<0.001）、UACR（从326±61mg/g改善至142±47mg/g，而DPP-4i组从345±48mg/g改善至306±60mg/g，P<0.01）和PWV（从11.77±2.37m/s改善至10.7±2.29m/s，而DPP-4i组从10.64±2.44m/s改善至10.54±2.84m/s，P<0.001）方面显示出更大改善，而只有联合治疗在cSBP方面有改善（从130.21±17.23mmHg改善至123.36±18.42mmHg）。这些效果与血糖控制无关。两种治疗均改善了GLS，但联合治疗的效果与DPP-4i相比显著更高（分别为18.19%和6.01%）。度拉糖肽和达格列净十二个月的治疗在动脉僵硬度、内皮功能、心肌功能和蛋白尿方面比DPP-4抑制剂显示出更大改善。对于这些患者，应考虑早期启动联合治疗作为二甲双胍的附加治疗。
