Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Department of Clinical Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Diabetologia. 2024 Dec;67(12):2637-2649. doi: 10.1007/s00125-024-06265-7. Epub 2024 Sep 14.
AIMS/HYPOTHESIS: Dipeptidyl peptidase-4 (DPP-4) inhibition has beneficial effects on various metabolic indicators in diabetes. Stromal cell-derived factor-1 (SDF-1) is expressed in diverse organs including the kidneys and is cleaved and inactivated by DPP-4 enzyme. The aim of this study was to conduct a randomised controlled trial to assess the effect of sitagliptin on diabetic nephropathy when used as an add-on therapy to the advanced hybrid closed-loop (AHCL) system in adolescents with type 1 diabetes and nephropathy.
This open-label, parallel-group, randomised controlled trial took place at the Pediatric Diabetes Clinic, Ain Shams University, Egypt. Forty-six adolescents aged 14.13 ± 2.43 years on the MiniMed 780G system for at least 6 months before study, with HbA ≤69 mmol/mol (8.5%) and diabetic nephropathy in the form of microalbuminuria, were randomly assigned to two groups (n=23 for each) based on a computer-generated randomisation sequence. The intervention group received oral sitagliptin 50 mg for 3 months. The other group used AHCL only and served as a control group. The primary outcome measure was the change in urinary albumin/creatinine ratio (UACR) after 3 months of administration of sitagliptin. The key secondary outcome measure was the change from baseline in SDF-1 levels after treatment.
Data for all participants were analysed. No significant difference was found between the groups as regards baseline clinical and laboratory characteristics as well as AHCL system settings (p>0.05). Serum SDF-1 levels were higher in all individuals with type 1 diabetes vs healthy control individuals (p<0.001). After 3 months, sitagliptin resulted in a significant decrease of SDF-1 levels from 3.58 ± 0.73 to 1.99 ± 0.76 ng/ml (p<0.001), together with improvement of UACR from 7.27 ± 2.41 to 1.32 ± 0.31 mg/mmol (p<0.001). In addition, sitagliptin reduced postprandial glucose, sensor glucose, coefficient of variation and total daily dose of insulin, while time in range 3.9-10.0 mmol/l (70-180 mg/dl) and insulin-to-carbohydrate ratio were significantly increased. Sitagliptin was safe and well-tolerated without severe hypoglycaemia or diabetic ketoacidosis.
CONCLUSIONS/INTERPRETATION: Sitagliptin as an add-on therapy to AHCL had a reno-protective effect for individuals with type 1 diabetes and diabetic nephropathy, in addition to the improvement of time in range while reducing glycaemic variability and without compromising safety.
This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
ClinicalTrials.gov NCT06115460.
目的/假设：二肽基肽酶-4（DPP-4）抑制剂对糖尿病的各种代谢指标均有有益影响。基质细胞衍生因子-1（SDF-1）在包括肾脏在内的多种器官中表达，并被 DPP-4 酶切割和失活。本研究的目的是进行一项随机对照试验，评估西他列汀作为附加疗法用于患有 1 型糖尿病和肾病的青少年的高级混合闭环（AHCL）系统时对糖尿病肾病的影响。
这项开放标签、平行组、随机对照试验在埃及艾因夏姆斯大学儿科糖尿病诊所进行。46 名年龄在 14.13±2.43 岁的青少年，在研究前至少使用 MiniMed 780G 系统 6 个月，HbA≤69 mmol/mol（8.5%），并患有以微量白蛋白尿为特征的糖尿病肾病，根据计算机生成的随机序列分为两组（每组 23 人）。干预组接受口服西他列汀 50mg 治疗 3 个月。另一组仅使用 AHCL 作为对照组。主要结局指标是西他列汀治疗 3 个月后尿白蛋白/肌酐比值（UACR）的变化。关键次要结局指标是治疗后 SDF-1 水平从基线的变化。
对所有参与者的数据进行了分析。两组间的基线临床和实验室特征以及 AHCL 系统设置均无显著差异（p>0.05）。所有 1 型糖尿病患者的血清 SDF-1 水平均高于健康对照组（p<0.001）。3 个月后，西他列汀使 SDF-1 水平从 3.58±0.73 降至 1.99±0.76ng/ml（p<0.001），同时 UACR 从 7.27±2.41 改善至 1.32±0.31mg/mmol（p<0.001）。此外，西他列汀降低了餐后血糖、传感器血糖、变异系数和胰岛素总日剂量，而 3.9-10.0mmol/l（70-180mg/dl）范围内的时间和胰岛素-碳水化合物比值显著增加。西他列汀安全且耐受良好，无严重低血糖或糖尿病酮症酸中毒发生。
结论/解释：西他列汀作为 AHCL 的附加疗法，对 1 型糖尿病和糖尿病肾病患者具有肾脏保护作用，同时改善了血糖控制范围，降低了血糖变异性，且不影响安全性。
本研究未从任何公共、商业或非营利性部门的资助机构获得特定的资助。
ClinicalTrials.gov NCT06115460。
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