Effect of Dapagliflozin on Post-Transplant Diabetes Mellitus and Kidney Allograft Function in Kidney Transplant Recipients: A Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective is to determine the effect of oral dapagliflozin compared to placebo, as an add-on to standard-of-care, on the incidence of post-transplant diabetes mellitus in non-diabetic kidney transplant recipients. 3

Secondary objectives include the evaluation of the following parameters:

• Prediabetes status
• Urinary albumin-to-creatinine ratio
• Incidence of urinary tract infections
• Renal function parameters
• Cardiovascular parameters
• Adverse events

The sponsor did not provide the total number of participants. The study population consists of kidney transplant recipients who are non-diabetic. Eligible participants include both males and females aged 18 years or older. Key inclusion requirements involve an estimated glomerular filtration rate greater than 25 ml/min/1.73m² within the three months prior to randomization and an immunosuppressive regimen that includes tacrolimus.

This phase 4, randomized, double-blind, placebo-controlled, national multicenter trial evaluates the effect of oral dapagliflozin compared to a placebo as an add-on to standard-of-care in kidney transplant recipients. The primary objective is to determine the incidence of post-transplant diabetes mellitus in non-diabetic patients. Eligible participants include adults with an estimated glomerular filtration rate (eGFR) greater than 25 ml/min/1.73m2 within three months prior to randomization and an immunosuppressive regimen including tacrolimus. The study protocol involves a screening visit to assess inclusion criteria, followed by treatment and follow-up visits at 6 and 12 months to monitor clinical outcomes such as prediabetes incidence, proteinuria, and renal composite outcomes. The total duration of the study period is estimated to span from March 2026 to May 2029.

The experimental medication consists of dapagliflozin, administered as 10 mg film-coated tablets via oral use. This substance is investigated as an add-on to standard-of-care therapy.

The placebo is an inactive substance administered through oral use. The placebo tablet is white, round, and biconvex with a diameter of 8 mm, composed of lactose monohydrate, potato starch, gelatin A, purified water, magnesium stearate, and talc. To maintain the double-blind design, these tablets are over-encapsulated in an opaque hard gelatin capsule that is identical in appearance to the capsule containing the active medication.

The primary efficacy endpoint is the incidence of post-transplant diabetes mellitus, which will be assessed following 6 and 12 months of follow-up. Secondary endpoints include the incidence of prediabetes, changes in the estimated glomerular filtration rate (eGFR), and proteinuria measured by the urine albumin-to-creatinine ratio (U-ACR).

Additional assessments conducted at the 6 and 12 month intervals involve:

• Changes in creatinine and cholesterol levels.
• Incidence of urinary tract infection determined by positive urine culture.
• Incidence of biopsy-verified kidney transplant rejection.
• Renal composite outcome, comprising the incidence of graft failure, end-stage renal disease (ESRD), or a creatinine increase exceeding 25%.
• Changes in systolic blood pressure and diastolic blood pressure.
• Relative incidence of out-of-target tacrolimus levels.
• Urine biomarkers indicative of podocyte and tubular function.
• Incidence of major adverse cardiac events (MACE) and all-cause mortality.
• Changes in the Short Form Health Survey 36 score from baseline to 12 months.
• Incidence of adverse events, serious adverse events, and serious adverse reactions.