Effect of Dorzagliatin on Renal Function Outcomes in People With Type 2 Diabetes: a Multicentric, Prospective, Randomized Study.

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.

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetic Nephropathy Type 2
• Intervention / Treatment: Drug: Dorzagliatin; Drug: Gliclazide

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.

• Study Type: Interventional
• Enrollment (Estimated): 106
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Division of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients treat with Dorzagliatin; Dorzagliatin will be initiated and maintained at 75mg twice a day until the completion of the study. Meanwhile, all patients will also continue on regimen of metformin 500mg three times a day throughout the study. Visits at 4-week intervals will be performed to evaluate the safety of drugs.	Drug: Dorzagliatin; Dorzagliatin will be initiated and maintained at 75mg twice a day
Active Comparator: Patients treat with Gliclazide; Gliclazide will be initiated and maintained at 30mg once a day until the completion of the study. Meanwhile, all patients will also continue on regimen of metformin 500mg three times a day throughout the study. Visits at 4-week intervals will be performed to evaluate the safety of drugs.	Drug: Gliclazide; Gliclazide will be initiated and maintained at 30mg once a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants' personal information	Self-reported information (age in years, gender，course of disease )	1 day
Physical assessments	BMI (body mass index) in kg/m^2	1 day
renal function	changes of renal function (eGFR, creatinine, cystatin C, TNF-1)	1 day
renal magnetic resonance imaging(MRI)	Changes of perirenal fat content, renal proton density fat fraction and degree of renal fibrosis	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
blood sugar	fasting blood sugar、2-hour postprandial blood sugar	1 day
insulin	fasting insulin、2-hour insulin	1 day
HOMA2-β	20*fasting insulin（mIU/L）/（fasting blood sugar（mmol/L）-3.5）	1 day
HOMA2-IR	fasting blood sugar（mmol/L）*fasting insulin（mIU/L）/22.5	1 day
HOMA2-IS	22.5/fasting blood sugar（mmol/L）*fasting insulin（mIU/L）	1 day

Collaborators and Investigators

• Sponsor: Yan Bi

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): February 20, 2024
• Primary Completion (Estimated): May 31, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: January 16, 2024
• First Submitted That Met QC Criteria: January 16, 2024
• First Posted (Actual): January 24, 2024

Study Record Updates

• Last Update Posted (Actual): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 16, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetic Nephropathies; Hypoglycemic Agents; Physiological Effects of Drugs; Gliclazide
• Other Study ID Numbers: BY2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No