The DPP-4 inhibitor sitagliptin improves glycaemic control and early-stage diabetic nephropathy in adolescents with type 1 diabetes using the MiniMed 780G advanced hybrid closed-loop system: a randomised controlled trial

Abstract

Abstract 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. Methods 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 HbA1c ≤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. Results 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. Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Trial registration ClinicalTrials.gov NCT06115460. Graphical abstract