Long-term allograft function in kidney transplant recipients (KTRs) remain suboptimal, and graft failure causes significant morbidity and mortality, with cardiovascular disease being the leading cause of death in KTRs and the most common cause of death with a functioning graft. Sodium-glucose cotransporter 2 (SGLT2) inhibitors safely lower cardiovascular and kidney disease risk in the non-transplant population, yet data in KTRs are lacking. This clinical trial seeks to establish the efficacy and safety of dapagliflozin, a SGLT2 inhibitor, for improving cardiovascular and kidney graft function in adult KTRs with type 2 diabetes and post-transplant diabetes, and to leverage innovate translational methods to define the underlying mechanisms of action.

Inclusion Criteria:

• Age 18-80 years
• Kidney transplant received 1 year prior to randomization
• estimated glomerular filtration rate 30-90 ml/min/1.73m2
• Urine albumin to creatinine ratio (ACR) 30-5000 mg/g
• Pre-existing type 2 diabetes or post-transplant diabetes mellitus
• Blood pressure <130/80 mm Hg prior to randomization
• Able to provide informed consent
• Stable immunosuppression for at least 3 months prior to baseline consisting of tacrolimus, mycophenolate mofetil/mycophenolic acid and prednisone
• Stable anti-hypertensive regimen for at least 1month prior to baseline
• Stable diabetes management for at least 3 months prior to baseline
• Stable angiotensin converting enzyme inhibitor/angiotensin receptor blocker use for at least 3 months prior to baseline (if applicable)
• Glucagon-like peptide-1 receptor agonist (GLP-1RA) for at least 3 months prior to baseline (if applicable)

Exclusion Criteria:

• Type 1 diabetes
• Anticipated life expectancy <1 year
• Uncontrolled hypertension
• Hemoglobin A1c >9%
• Body mass index >40 kg/m2
• New York Heart Association Class 3 or 4 heart failure symptoms, an EF ≤30%, or hospitalization for heart failure in the past 3 months
• Pregnancy, plans to become pregnant, or breastfeeding
• Current use of sodium glucose cotransporter-2 (SGLT2) inhibitors
• Current urinary or urogenital infection
• Use of anticoagulants (contraindication to kidney biopsy)
• Magnetic resonance imaging (MRI) contraindications
• History of lower-limb amputation irrespective of etiology
• Known hypersensitivity to dapagliflozin

At the conclusion of the study, data, which has been stripped of all personal identification information and coded with a number, will be made available to qualified individuals within the scientific community who apply for data use. The results and outcomes of this study will be made generally available by publication and journal articles submitted to PubMed Central in compliance with NIH access guidelines.

At the conclusion of the study, data, which has been stripped of all personal identification information and coded with a number, will be made available to qualified individuals within the scientific community who apply for data use. The results and outcomes of this study will be made generally available by publication and journal articles submitted to PubMed Central in compliance with NIH access guidelines.