Efficacy and Safety of Empagliflozin in NODAT

Efficacy and Safety of Empagliflozin Compared With Linagliptin in New-onset Diabetes Mellitus After Kidney Transplantation

This is an open label, randomized controlled study. We'd like to access the safety and effects of empagliflozin compared with linagliptin in new-onset diabetes after kidney transplantation patients. Our primary endpoints are kidney related indicators and secondary endpoints are glucose and lipid metabolism related indicators and adverse events. We are going to recruit 35 patients for each group and follow six months.

Study Overview

• Status: Terminated
• Conditions: Kidney Transplant; Complications; New Onset Diabetes After Transplant
• Intervention / Treatment: Drug: Empagliflozin; Drug: Linagliptin

Detailed Description

In recent years, with the development of transplantation technology and immunosuppressive agents, kidney transplantation has made considerable progress. However, for metabolic disorders after kidney transplantation, such as new diabetes after kidney transplantation, there is still insufficient awareness. Since 1964, Starlz et al. first discovered and proposed New-onset diabetes after kidney transplantation（NODAT） in patients after renal transplantation. Scholars from all countries have paid considerable attention to it. The Chinese guidelines indicate that NODAT can increase the risk of graft-related complications, such as rejection, graft loss and infection, and ultimately affect the long-term survival of the recipient. In addition, NODAT has also been shown to increase the risk of cardiovascular events, and cardiovascular disease is associated with more than half of kidney transplant deaths. A retrospective study of 567 renal transplant recipients in China showed that the incidence of NODAT was 24.2%. It can be seen that the incidence of new-onset diabetes after renal transplantation is high and has long-term adverse effects on transplant patients. Therefore, there is an urgent need to evaluate and investigate NODAT's therapeutic drug regimens.

According to the study, empagliflozin has a protective effect on the kidney and cardiovascular system, but it has not yet been written into the treatment guidelines for new-onset diabetes after kidney transplantation. Metformin and linagliptin are frequently used in diabetics after renal transplantation, and linagliptin also have a protective effect on the kidneys. Therefore, this experiment wanted to compare the effects between empagliflozin and linagliptin on kidney protection.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Shan Mou, Dr.; Phone Number: +8613918221242; Email: shan_mou@126.com
• Study Contact Backup: Name: Yaomin Hu, Dr.; Phone Number: +86‭13651617002‬; Email: amin99@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200127
      • Department of nephrology, endocrinology and kidney transplantation , Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Single kidney transplantation
• Normal glucose tolerance or Pre-Diabetes mellitus before transplantation
• According to Oral glucose tolerance test results to make the diagnosis of NODAT
• Standard triple immunosuppression therapy
• HbA1c≤10%
• Steady hormone usage
• BMI 18.5-30kg/m2
• Patient informed consent

Exclusion Criteria:

• Diabetes patients before transplantation
• Pregnancy pregnancy
• Type 1 diabetes after kidney transplantation
• Severe liver function impairment (AST/ALT 3 times standard value)
• Severely impaired renal function (eGFR<45)
• Having uncontrolled diseases
• History of cancer in the past 5 years (except basal cell carcinoma) and/or cancer treatment
• Participating in another trial involving the study drug with in 30 days
• Premenopausal women (1 year before the last menstrual period ≤ informed consent)
• Alcohol or drug abuse within 3 months of informed consent, affecting compliance Need other drugs to control NODAT

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Empagliflozin; Jardiance 10mg/25mg Film-coated tablets， once daily	Drug: Empagliflozin; Dosage adjustment based on glucose targets . Once daily; Other Names: Jardiance
Active Comparator: Linagliptin; Trajenta 5mg Film-coated tablets， once daily	Drug: Linagliptin; Dosage adjustment based on glucose targets. Once daily; Other Names: Tradjenta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
eGFR	the change from baseline in estimated glomerular filtration rate calculated by MDRD formula	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Graft loss rate	the frequency of patients' graft loss or dysfunction	24 weeks
Mortality rate	the patients' death rate related to treatment and transplantation with in 24 weeks after treatment	24 weeks
Acute rejection	the frequency of acute rejection	24 weeks
Progression to albuminuria	the frequency of macroalbuminuria	24 weeks
Progression to macroalbuminuria	the frequency of macroalbuminuria	24 weeks
Fasting plasma glucose	Change from baseline in fasting plasma glucose	24 weeks
Glycated hemoglobin (HbA1c)	Change from baseline in HbA1c	24 weeks
Adverse events	Record adverse events that related to treatment and transplantation	24 weeks

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Investigators: Study Chair: Zhaohui Ni, Dr., Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Study Director: Shan Mou, Dr., Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Principal Investigator: Yaomin Hu, Dr., Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Principal Investigator: Ming Zhang, Dr., Renji Hospital, School of Medicine, Shanghai Jiao Tong University

Publications and helpful links

General Publications

• Lo C, Toyama T, Oshima M, Jun M, Chin KL, Hawley CM, Zoungas S. Glucose-lowering agents for treating pre-existing and new-onset diabetes in kidney transplant recipients. Cochrane Database Syst Rev. 2020 Jul 30;8(8):CD009966. doi: 10.1002/14651858.CD009966.pub3.

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2018
• Primary Completion (Actual): January 31, 2019
• Study Completion (Actual): January 31, 2019

Study Registration Dates

• First Submitted: July 16, 2018
• First Submitted That Met QC Criteria: August 20, 2018
• First Posted (Actual): August 22, 2018

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 22, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: diabetes; kidney transplantation; empagliflozin; linagliptin
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Empagliflozin; Linagliptin
• Other Study ID Numbers: RJ20180601NODAT

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes