Clinical trial NCT03642184: Efficacy and Safety of Empagliflozin in NODAT
Official title: Efficacy and Safety of Empagliflozin Compared With Linagliptin in New-onset Diabetes Mellitus After Kidney Transplantation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: New Onset Diabetes After Transplant
Kidney Transplant; Complications
Keywords: empagliflozin
linagliptin
diabetes
kidney transplantation
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
First posted: 2018-08-22
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: eGFR
timeFrame: 24 weeks
Secondary outcomes:
measure: Graft loss rate
timeFrame: 24 weeks
measure: Mortality rate
timeFrame: 24 weeks
measure: Acute rejection
timeFrame: 24 weeks
measure: Progression to albuminuria
timeFrame: 24 weeks
measure: Progression to macroalbuminuria
timeFrame: 24 weeks
measure: Fasting plasma glucose
timeFrame: 24 weeks
measure: Glycated hemoglobin (HbA1c)
timeFrame: 24 weeks
measure: Adverse events
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Department of nephrology, endocrinology and kidney transplantation , Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine
state: Shanghai
Study officials:
affiliation: Renji Hospital, School of Medicine, Shanghai Jiao Tong University
name: Zhaohui Ni, Dr.
role: STUDY_CHAIR
affiliation: Renji Hospital, School of Medicine, Shanghai Jiao Tong University
name: Shan Mou, Dr.
role: STUDY_DIRECTOR
affiliation: Renji Hospital, School of Medicine, Shanghai Jiao Tong University
name: Yaomin Hu, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Renji Hospital, School of Medicine, Shanghai Jiao Tong University
name: Ming Zhang, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.