SGLT2i Effect on PTDM Development and Kidney Allograft Function in Non-diabetic Kidney Transplant Recipients: A Randomized, Doubleblind, Placebo Controlled, National Multicenter Trial (SGL-TX-PTDM)

SGL-TX-PTDM: SGLT2i Effect on PTDM Development and Kidney Allograft Function in Kidney Transplant Recipients: A Randomized, Doubleblind, Placebo Controlled, National Multicenter Trial

The goal of this clinical trial is to find out whether 12 months of treatment with the SGLT2 inhibitor Forxiga® (dapagliflozin 10 mg once daily), compared with placebo, can reduce the risk of developing post-transplant diabetes in kidney transplant recipients who do not have diabetes at the time of transplantation.

The main questions it aims to answer are:

• Does Forxiga reduce the risk of developing post-transplant diabetes and prediabetes compared with placebo?
• Does Forxiga help preserve the function of the transplanted kidney compared with placebo?
• Is Forxiga safe for kidney transplant recipients who do not have diabetes?
• Does Forxiga affect the occurrence of urinary tract infections, the amount of protein in the urine, and other kidney- and heart-related health measures compared with placebo?

Researchers will compare Forxiga with a placebo (a look-alike tablet containing no active medicine) to see whether it can reduce the risk of post-transplant diabetes while maintaining kidney function and remaining safe to use.

Adults who have recently received a kidney transplant and do not have diabetes may take part if they meet the study requirements.

Participants will be randomly assigned to receive either Forxiga or placebo once daily for 12 months. They will attend study visits 3, 6, and 12 months after joining the study. These visits will include health checks, blood tests, and urine tests. Neither the participants nor the study doctors will know which treatment each participant is receiving.

Study Overview

• Status: Not yet recruiting
• Conditions: Post Transplant Diabetes Mellitus; Kidney Transplant Recipient; Placebo Control Design; Non-Diabetic Patients; Sodium Glucose Co-Transporter 2 Inhibitors; Randomized Controlled Trial (RCT)
• Intervention / Treatment: Drug: SGLT2i; Drug: Placebo

Detailed Description

Background Kidney transplantation is the best treatment of end-stage renal disease (ESRD), although median allograft survival is only 15 years. In non-transplant patients with chronic kidney disease (CKD) sodium-glucose co-transporter type 2 inhibitors (SGLT2i) protects kidney function and reduces decline in estimated glomerular filtration (eGFR) and in KTR with PTDM, SGLT2i improve glucose regulation.

Perspective With the current kidney transplant survival of average 15 years, app. one out of ten adult[1] kidney transplant recipients (KTR) outlive their donated kidneys. This poses a significant burden to the patients and society and increases the demand for new transplantations. WHO reported a 9% increase in the number of kidney transplant recipients from 2022 to 2023[2]. The growing population of kidney transplant recipients underscores the importance of research aimed at prolonging graft survival and preventing post-transplant diabetes mellitus (PTDM). The efficacy of SGLT2i on reducing PTDM incidence remain untested in KTR.

The SGL-TX-PTDM study aim to investigate the effect of SGLT2i on the incidence of PTDM. PTDM is associated with a 63% increased risk for graft failure and an 87% increased risk for death[8]. PTDM is therefore known to be a threat to graft and patient survival throughout many years [9]. In the long-term perspective, we hope to contribute with knowledge to preserve kidney transplant function, benefit society, and improve patients' quality of life.

Hypothesis We hypothesize that SGLT2i will reduce the incidence of PTDM in non-diabetic KTR as an add-on to standard-of-care.

Research Objective In this superior randomized controlled clinical trial we will determine the effect of oral SGLT2i compared with placebo as add-on to standard-of-care on incidence of PTDM in non-diabetic KTR.

The secondary objectives will evaluate the effect of oral SGLT2i on prediabetes status, eGFR, U-ACR, urinary tract infection, renal parameters, cardiovascular parameters and adverse events in non-diabetic KTR.

Design An investigator-initiated, placebo-controlled, double-blinded, parallel-group, randomized, national, multicenter intervention study.

Methods Adults without pre-existing diabetes who are admitted for kidney transplantation will be screened for eligibility and invited to participate. Written informed consent will be obtained prior to any study-specific procedures. When the kidney allograft achieves an estimated glomerular filtration rate (eGFR) of 25 mL/min, eligible participants will be randomized in a 1:1 allocation ratio to receive either 12 months of oral SGLT2 inhibitor therapy (Dapagliflozin 10 mg once daily) or a matching placebo. Study medication will be administered in addition to standard immunosuppressive therapy.

Participants will continue to receive routine post-transplant clinical care throughout the study period. Study assessments will be conducted at baseline and at 3, 6, and 12 months following randomization. Clinical evaluations will include blood and urine laboratory tests, with safety and efficacy monitored at each visit by the treating nephrologist.

Post-transplant diabetes mellitus (PTDM) will be assessed according to the diagnostic criteria of the American Diabetes Association (ADA). All study procedures, data collection time points, and outcome assessments follow the SPIRIT 2025 guidance for interventional trial protocols.

Primary endpoint

• PTDM incidence after 3, 6 and 12 month follow up. , defined as any of the following criteria (HbA1c ≥ 48 mmol/mol or Fasting plasma glucose ≥ 7.0 mmol/L or random plasma glucose ≥ 11.1 mmol/L)

Secondary endpoint

• Prediabetes status after 3,6 and 12 month follow up, defined as any of the following criteria (HbA1c between 39-47 mmol/mol or Impaired fasting plasma glucose between 5.6-6.9 mmol/L or Continuous glucose monitoring mean blood glucose time above range 7,8 mmol/L

  ▪ Kidney allograft function (eGFR) change after 3, 6 and 12 month follow up.

• Albumin/creatinine ratio (U-ACR) (mg/g), after 3, 6 and 12 month follow up.
• Blood samples after 3, 6 and 12 month follow up. (Creatinine (umol/L, Total-Cholesterol, Low-and high-density lipoproteins (LDL and HDL, respectively) and triglycerides, Clinical routine Tacrolimus concentration (ug/L))
• Urinary tract infection (positive culture) incidence after 3, 6 and 12 month follow up.
• Incidence of kidney transplant rejection (biopsy verified) after 3, 6 and 12 month follow up.
• Renal composite outcome after 3, 6 and 12 month follow up. (Incidence of graft failure - defined as return to dialysis or retransplantation or Incidence of ESRD (defined as eGFR<15 ml/min/1.73m2) or Incidence of > 25% increase in creatinine
• Change in Systolic blood pressure (SysBP) (mmHg) and diastolic blood pressure (DiaBP) (mmHg), after 3, 6 and 12 month follow up.
• Relative incidence of out-of-target measures of clinical routine blood Tacrolimus levels
• Urine biomarkers indicative of podocyt and tubular function from selected sites
• Incidence of: Adverse events, Serious adverse events, Serious adverse reactions, Death - all cause mortality, and Major Adverse Cardiac Events (MACE)

Tertiary endpoints

• SF-36 (Short Form Health Survey 36)

Study population A total of 184 adults without pre-existing diabetes who undergo kidney transplantation will be recruited from three Danish transplant centers: Odense University Hospital (OUH), Aarhus University Hospital (AUH), and Copenhagen University Hospital - Rigshospitalet (RH). Participants will be enrolled once the kidney allograft has achieved an estimated glomerular filtration rate (eGFR) ≥ 25 mL/min. Eligible participants will then be randomized to receive either a daily dose of SGLT2 inhibitor or matching placebo for 12 months following randomization.

• Study Type: Interventional
• Enrollment (Estimated): 184
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lotte B Lange, MD; Phone Number: +45 40863392; Email: Lotte.Borg.Lange@rsyd.dk

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Department of Renal Medicine
    • Contact: Henrik Birn, Head of research; Phone Number: +45 40460831; Email: hb@clin.au.dk
  • Copenhagen, Denmark, 2100
    • Department of Nephrology and Endocrinology.
    • Contact: Mads Hornum, Head of research; Phone Number: +45 35459608; Email: Mads.Hornum@regionh.dk
  • Odense, Denmark, 5000
    • Department of Nephrology, Odense University Hospital
    • Contact: Lotte B Lange, MD; Phone Number: +45 40863392; Email: Lotte.Borg.Lange@rsyd.dk

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Obtained written informed consent
• Male or female patients, age ≥ 18 years.
• Non-diabetic KTR
• Immunosuppressive must include Tacrolimus

Exclusion Criteria:

• Patients who is treated (diet or antidiabetics) for diabetes type 1 or 2 before randomization
• eGFR< 25 ml/min/1.73m2 (before randomization)
• Alanine aminotransferase (ALAT) > 3 x upper normal limit
• Bilirubin > 2 x upper normal limit
• Pregnancy
• Positive plasma hCG
• Breastfeeding
• Known allergy towards SGLT2i or the content substance
• Patients with chronic intestinal diseases, including inflammatory bowel diseases (e.g., Crohn's disease and ulcerative colitis) and structural conditions such as short bowel syndrome.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: SGLT2i; Daily dose of SGLT2i (Forxiga 10 mg tablet)	Drug: SGLT2i; The intervention in this clinical trial will be treatment with an SGLT2 inhibitor (Forxiga, 10 mg tablet once daily) compared with a matching placebo. A total of 184 non-diabetic kidney transplant recipients will be enrolled. All participants will be randomized in a 1:1 ratio to receive either Forxiga or placebo as an add on to standard immunosuppressive therapy. This intervention differs from other studies by specifically targeting non-diabetic kidney transplant recipients, a population in which the efficacy and safety of SGLT2 inhibitors have not yet been established.; Other Names: Dapagliflozin; Forxiga 10 mg
Placebo Comparator: Placebo; Daily dose of placebo tablet	Drug: Placebo; The control intervention in this clinical trial will be a matching placebo tablet, identical in appearance to Forxiga (10 mg), administered once daily as an add on to standard immunosuppressive therapy. A total of 184 non-diabetic kidney transplant recipients will be enrolled. All participants will be randomized in a 1:1 ratio to receive either placebo or Forxiga. This placebo intervention ensures blinding of both participants and investigators and allows a direct comparison of the safety and efficacy of SGLT2 inhibition versus no active treatment in this unique patient population.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of post-transplant diabetes mellitus (PTDM)	Domain: Post-transplant diabetes mellitus Specific measurement: Diagnosis of PTDM according to the American Diabetes Association (ADA) diagnostic criteria. Specific metric: Number of participants with PTDM Method of aggregation: Proportion of participants with PTDM in each treatment group (dapagliflozin versus placebo) Time point: 3, 6 and 12 months after randomization	Follow up at 3,6 and 12 months after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prediabetes status	Domain: Prediabetes Specific measurement: Prediabetes defined as HbA1c 39-47 mmol/mol, impaired fasting plasma glucose 5.6-6.9 mmol/L. Specific metric: Number of participants with prediabetes Method of aggregation: Proportion of participants with prediabetes in each treatment group (dapagliflozin versus placebo) Time point: 3, 6 and 12 months after randomization	Follow up at 3,6 and 12 months after randomization
Change in kidney allograft function	Domain: Kidney allograft function Specific measurement: Estimated glomerular filtration rate (eGFR), calculated using the CKD-EPI equation (mL/min/1.73 m²). Specific metric: Change from baseline Method of aggregation: Mean change from baseline in each treatment group (dapagliflozin versus placebo) Time point: 3, 6 and 12 months after randomization	Follow up at 3,6 and 12 months after randomization
Change in proteinuria	Domain: Proteinuria Specific measurement: Urine albumin-to-creatinine ratio (U-ACR), expressed as mg/g. Specific metric: Change from baseline Method of aggregation: Mean change from baseline in each treatment group (dapagliflozin versus placebo) Time point: 3, 6 and 12 months after randomization	Follow up at 3,6 and 12 months after randomization
Change in biochemical parameters	Domain: Biochemical parameters Specific measurement: Serum creatinine (µmol/L), total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and tacrolimus trough concentration (µg/L). Specific metric: Change from baseline Method of aggregation: Mean change from baseline in each treatment group (dapagliflozin versus placebo) Time point: 3, 6 and 12 months after randomization	Follow up at 3,6 and 12 months after randomization
Urinary tract infections	Domain: Urinary tract infections Specific measurement: Positive urine cultures confirming urinary tract infection. Specific metric: Total number of urinary tract infection episodes Method of aggregation: Total number of urinary tract infection episodes in each treatment group (dapagliflozin versus placebo) Time point: 3, 6 and 12 months after randomization	Follow up at 3,6 and 12 months after randomization
Kidney transplant rejection	Domain: Kidney transplant rejection Specific measurement: Biopsy-verified kidney transplant rejection. Specific metric: Number of participants with at least one biopsy-verified kidney transplant rejection episode Method of aggregation: Proportion of participants with at least one biopsy-verified rejection episode in each treatment group (dapagliflozin versus placebo) Time point: 3, 6 and 12 months after randomization	Follow up at 3,6 and 12 months after randomization
Renal composite outcome	Domain: Renal composite outcome Specific measurement: Occurrence of any of the following: graft failure (defined as return to dialysis or kidney retransplantation), end-stage kidney disease (defined as eGFR <15 mL/min/1.73 m²), or a >25% increase in serum creatinine from baseline. Specific metric: Number of participants experiencing the renal composite outcome Method of aggregation: Proportion of participants experiencing the renal composite outcome in each treatment group (dapagliflozin versus placebo) Time point: 3, 6, and 12 months after randomization	Follow up at 3,6 and 12 months after randomization
Change in blood pressure	Domain: Blood pressure Specific measurement: Systolic blood pressure and diastolic blood pressure, measured in mmHg. Specific metric: Change from baseline Method of aggregation: Mean change from baseline in each treatment group (dapagliflozin versus placebo) Time point: 3, 6 and 12 months after randomization	Follow up at 3,6 and 12 months after randomization
Out-of-target tacrolimus trough concentrations	Domain: Tacrolimus trough concentrations Specific measurement: Clinical routine tacrolimus trough concentration >6 µg/L. Specific metric: Number of participants with at least one out-of-target tacrolimus trough concentration Method of aggregation: Proportion of participants with at least one out-of-target tacrolimus trough concentration in each treatment group (dapagliflozin versus placebo) Time point: 3, 6, and 12 months after randomization	Follow up at 3,6 and 12 months after randomization
Change in urinary biomarkers indicative of podocyte and tubular function	Domain: Urinary biomarkers of podocyte and tubular function Specific measurement: Urinary biomarkers indicative of podocyte and tubular function (e.g., NGAL and KIM-1) measured in participants from selected study sites. Specific metric: Change from baseline Method of aggregation: Mean change from baseline in each treatment group (dapagliflozin versus placebo) Time point: Baseline and 6 months after randomization	Baseline and 6 months follow up
Incidence of adverse events, serious adverse events, serious adverse reactions, all-cause mortality, and major adverse cardiovascular events (MACE)	Domain: Safety Specific measurement: Incidence of adverse events (AEs), serious adverse events (SAEs), serious adverse reactions (SARs), all-cause mortality, and major adverse cardiovascular events (MACE). Specific metric: Number of participants experiencing one or more safety events Method of aggregation: Proportion of participants experiencing one or more safety events in each treatment group (dapagliflozin versus placebo) Time point: 12 months after randomization	Follow up at 12 months after randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health-related quality of life	Domain: Health-related quality of life Specific measurement: Short Form Health Survey 36 (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. Specific metric: Change from baseline Method of aggregation: Mean change from baseline in each treatment group (dapagliflozin versus placebo) Time point: Baseline and 12 months after randomization	By baseline and 12 months after randomization

Collaborators and Investigators

• Sponsor: Odense University Hospital
• Collaborators: Aarhus University Hospital; Copenhagen University Hospital, Denmark
• Investigators: Principal Investigator: Lotte B Lange, MD, Department of Nephrology, Odense University Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): October 1, 2029

Study Registration Dates

• First Submitted: June 19, 2026
• First Submitted That Met QC Criteria: June 26, 2026
• First Posted (Actual): July 2, 2026

Study Record Updates

• Last Update Posted (Actual): July 2, 2026
• Last Update Submitted That Met QC Criteria: June 26, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: RCT; Kidney Transplant; SGLT2i; Kidney Transplant Recipients; non-diabetic patients; Sodium-glucose Transporter 2 inhibitors; SGL-TX-PTDM
• Additional Relevant MeSH Terms: dapagliflozin
• Other Study ID Numbers: EU CT:2024-518774-14-00; 2024-518774-14-00 (Ctis)

Plan for Individual participant data (IPD)

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

IPD Plan Description

Data Available:

Individual participant data (IPD) that underlie the results reported in the published article will be shared after de-identification. This includes text, tables, figures, and appendices.

Supporting Documents:

The study protocol and statistical analysis plan will also be made available.

Time Frame:

Data will be shared immediately following publication. There is no specified end date for availability.

Criteria for Access:

Data will be shared with researchers who submit a methodologically sound proposal aimed at achieving the goals outlined in their approved research proposal.

Access Mechanism:

Interested researchers should direct their proposals to:

lotte.borg.lange@rsyd.dk. To gain access, requestors will be required to sign a data access agreement.

Data Storage:

The data will be stored for 25 years on a secure third-party platform (OPEN).

IPD Sharing Time Frame

The data will be available after the last patients last visit.

Data Storage:

The data will be stored for 25 years on a secure third-party platform (OPEN).

IPD Sharing Access Criteria

Criteria for Access:

Data will be shared with researchers who submit a methodologically sound proposal aimed at achieving the goals outlined in their approved research proposal.

Interested researchers should direct their proposals to:

lotte.borg.lange@rsyd.dk. To gain access, requestors will be required to sign a data access agreement.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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