Clinical trial NCT06222476: Effect of Dorzagliatin on Renal Function Outcomes in People With Type 2 Diabetes: a Multicentric, Prospective, Randomized Study.
Official title: A Multicentric, Prospective, Randomized Study Evaluating the Improvement of Renal Function Outcomes With Dorzagliatin in Patients With Type 2 Diabetes Mellitus With Early Kidney Injury.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Diabetic Nephropathy Type 2
Lead sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Sponsor class: OTHER
First posted: 2024-01-24
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to explore the improvement of renal function before and after the intervention of dorzagliatin in patients with type 2 diabetes.

Detailed description: As soon，metformin、SGLT-2i、GLP-1RA have been confirmed to have protective effect on the kidneys in the statement of consensus at home and abroad. Dorzagliatin exerts a potent hypoglycemic effect by activating glucokinase and is not affected by the patient's renal function. However, previous studies of this drug have rarely involved studies that improve markers related to renal function. On the one hand, in this study, changes of renal function (eGFR, creatinine, cystatin C, TNF-1) are collected to investigate whether dorzagliatin is benefit to kidney. On the other hand, renal magnetic resonance imaging(MRI) results are analysed to explore the differences among control subjects and patients treated with dorzagliatin.

Eligibility criteria: Inclusion Criteria:

1. Age:18-75 years old, male and female.
2. Patients with type 2 diabetes mellitus, type 2 diabetes mellitus diagnosis criteria: according to the "Chinese Type 2 Diabetes Mellitus Prevention and Treatment Guide (2020 Edition).
3. UACR 30-299mg/g.
4. eGFR ≥60mL/min/1.73m².
5. HbA1c 7.0-10.5%.

Exclusion Criteria:

1. Pregnant and lactating women and women of childbearing age who do not want to take reliable contraceptive measures.
2. Known allergic history to dorzagliatin/gliclazide/metformin.
3. Diabetic acute and chronic complications, including diabetic ketoacidosis, a hyperglycemic hyperosmolar state or hypoglycemic coma, etc.
4. Serious impairment of heart, liver, kidney and other organs.
5. With hypertension(≥140/90mmHg).
6. Fasting C-peptide \<300pmol/L.
7. Contraindications of MRI examination, such as implantation of metal prosthesis in vivo, claustrophobia, wearing insulin pumps, etc.

Primary outcomes:
measure: Participants' personal information
timeFrame: 1 day
measure: Physical assessments
timeFrame: 1 day
measure: renal function
timeFrame: 1 day
measure: renal magnetic resonance imaging(MRI)
timeFrame: 1 day
Secondary outcomes:
measure: blood sugar
timeFrame: 1 day
measure: insulin
timeFrame: 1 day
measure: HOMA2-β
timeFrame: 1 day
measure: HOMA2-IR
timeFrame: 1 day
measure: HOMA2-IS
timeFrame: 1 day
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Division of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University
state: Jiangsu
Study officials:
References:
citation: Yang W, Zhu D, Gan S, Dong X, Su J, Li W, Jiang H, Zhao W, Yao M, Song W, Lu Y, Zhang X, Li H, Wang G, Qiu W, Yuan G, Ma J, Li W, Li Z, Wang X, Zeng J, Yang Z, Liu J, Liang Y, Lu S, Zhang H, Liu H, Liu P, Fan K, Jiang X, Li Y, Su Q, Ning T, Tan H, An Z, Jiang Z, Liu L, Zhou Z, Zhang Q, Li X, Shan Z, Xue Y, Mao H, Shi L, Ye S, Zhang X, Sun J, Li P, Yang T, Li F, Lin J, Zhang Z, Zhao Y, Li R, Guo X, Yao Q, Lu W, Qu S, Li H, Tan L, Wang W, Yao Y, Chen D, Li Y, Gao J, Hu W, Fei X, Wu T, Dong S, Jin W, Li C, Zhao D, Feng B, Zhao Y, Zhang Y, Li X, Chen L. Dorzagliatin add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial. Nat Med. 2022 May;28(5):974-981. doi: 10.1038/s41591-022-01803-5. Epub 2022 May 12.
citation: Simons PIHG, Simons N, Stehouwer CDA, Schalkwijk CG, Schaper NC, Brouwers MCGJ. Association of common gene variants in glucokinase regulatory protein with cardiorenal disease: A systematic review and meta-analysis. PLoS One. 2018 Oct 23;13(10):e0206174. doi: 10.1371/journal.pone.0206174. eCollection 2018.
citation: Hishida A, Takashima N, Turin TC, Kawai S, Wakai K, Hamajima N, Hosono S, Nishida Y, Suzuki S, Nakahata N, Mikami H, Ohnaka K, Matsui D, Katsuura-Kamano S, Kubo M, Tanaka H, Kita Y. GCK, GCKR polymorphisms and risk of chronic kidney disease in Japanese individuals: data from the J-MICC Study. J Nephrol. 2014 Apr;27(2):143-9. doi: 10.1007/s40620-013-0025-0. Epub 2013 Dec 17.
citation: Wang K, Shi M, Yang A, Fan B, Tam CHT, Lau E, Luk AOY, Kong APS, Ma RCW, Chan JCN, Chow E. GCKR and GCK polymorphisms are associated with increased risk of end-stage kidney disease in Chinese patients with type 2 diabetes: The Hong Kong Diabetes Register (1995-2019). Diabetes Res Clin Pract. 2022 Nov;193:110118. doi: 10.1016/j.diabres.2022.110118. Epub 2022 Oct 13.
citation: Lin L, Dekkers IA, Huang L, Tao Q, Paiman EHM, Bizino MB, Jazet IM, Lamb HJ. Renal sinus fat volume in type 2 diabetes mellitus is associated with glycated hemoglobin and metabolic risk factors. J Diabetes Complications. 2021 Sep;35(9):107973. doi: 10.1016/j.jdiacomp.2021.107973. Epub 2021 Jun 15.