Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand.
Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.
J Diabetes Res. 2021 Oct 16;2021:7382620. doi: 10.1155/2021/7382620. eCollection 2021.
Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control and have pleiotropic effects on kidney injury, albuminuria, and vascular inflammation, especially in animal models. We evaluated the effects of a potent DPP4 inhibitor (gemigliptin) on these processes among patients with diabetic kidney disease (DKD).
This study employed a multicenter, prospective, randomized, placebo-controlled design. A total of 201 participants were enrolled and randomly assigned to one of two groups, one received treatment with 50 mg gemigliptin daily along with standard care for diabetes mellitus for 6 months. The changes in the coronary calcium score (CAC score), cardio-ankle vascular index (CAVI), estimated glomerular filtration rate (eGFR), vascular calcification level, and tubular renal injury marker expression were evaluated at baseline and 6 months.
In total, 182 patients completed the study. Significant reductions in hemoglobin A1C levels were observed in both groups. The changes in the CAC score, CAVI, eGFR, and level of proteinuria over the 6 months of the study did not significantly differ between the gemigliptin and control groups. However, biomarkers of vascular calcification, including serum bone alkaline phosphatase and kidney injury, including urine neutrophil gelatinase-associated lipocalin (NGAL)/Cr and urine liver fatty acid-binding protein (L-FABP)/Cr, were improved significantly in the gemigliptin treatment group compared with the control group. No serious adverse events were observed during the study.
Our study showed that gemigliptin significantly improved the expression of renal tubular injury biomarkers and vascular calcification levels among patients with DKD; however, gemigliptin did not affect renal function or coronary calcification compared with those observed in the control. A larger study with a longer follow-up is essential to verify these beneficial effects. . This trial is registered with ClinicalTrials.Gov Identifier NCT04705506.
二肽基肽酶-4（DPP-4）抑制剂可改善血糖控制，并对肾脏损伤、蛋白尿和血管炎症具有多种作用，尤其在动物模型中。我们评估了一种强效 DPP4 抑制剂（西格列汀）在糖尿病肾病（DKD）患者中对这些过程的影响。
本研究采用多中心、前瞻性、随机、安慰剂对照设计。共纳入 201 名参与者，并随机分为两组，一组接受每日 50mg 西格列汀联合糖尿病标准治疗 6 个月，另一组接受安慰剂治疗。在基线和 6 个月时评估冠状动脉钙评分（CAC 评分）、心踝血管指数（CAVI）、估计肾小球滤过率（eGFR）、血管钙化水平和肾小管肾损伤标志物的表达变化。
共有 182 名患者完成了研究。两组的血红蛋白 A1C 水平均显著降低。在研究的 6 个月内，两组间 CAC 评分、CAVI、eGFR 和蛋白尿水平的变化无显著差异。然而，与对照组相比，西格列汀治疗组血管钙化标志物（包括血清骨碱性磷酸酶）和肾脏损伤标志物（包括尿中性粒细胞明胶酶相关脂质运载蛋白[NGAL]/Cr 和尿肝脂肪酸结合蛋白[L-FABP]/Cr）的表达显著改善。研究过程中未观察到严重不良事件。
我们的研究表明，西格列汀可显著改善 DKD 患者肾小管损伤标志物和血管钙化水平的表达；然而，与对照组相比，西格列汀对肾功能或冠状动脉钙化无影响。需要更大规模、随访时间更长的研究来验证这些有益效果。本试验在 ClinicalTrials.Gov 注册号为 NCT04705506。
