Efficacy and Safety of Empagliflozin in NODAT

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
New Onset Diabetes After Transplant, Kidney Transplant; Complications

Intervention / Treatment
-----------------
* Drug: Empagliflozin
* Drug: Linagliptin


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
empagliflozin, linagliptin, diabetes, kidney transplantation