Dapagliflozin for Renal Protection in Heart Transplant Recipients: A Randomized Clinical Trial

Background: Progressive kidney disease is common in heart transplant recipients due to calcineurin inhibitor exposure and pre-existing comorbidities. Sodium–glucose cotransporter-2 (SGLT2) inhibitors may attenuate the decline in kidney function, but evidence in heart transplant recipients is limited. Methods: The DAPAgliflozin for Renal protection in Heart Transplant recipients (DAPARHT) trial is a multicenter, double-blind, randomized, placebo-controlled trial conducted at six heart transplant centers in Northern Europe. We randomized adult heart transplant recipients with an estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73 m ² at least one year after transplantation 1:1 to receive dapagliflozin 10 mg or matching placebo once daily. The primary endpoint was the slope of the eGFR from 2 weeks after treatment initiation to the end of the 12-month blinded treatment period. Results: Between June 2022 and September 2025, we randomized 430 participants, of whom 217 were allocated to dapagliflozin and 213 were allocated to placebo. We included the 424 patients with at least one eGFR measurement after baseline in the full analysis set. Their mean age was 53 ± 14 years and 29& were women. The eGFR at baseline was 67 ± 22 mL/min/1.73 m 2 . The median time from transplantation was 7 (3 – 13) years. Dapagliflozin improved the chronic slope of the eGFR compared with placebo. The change in the eGFR from 2 weeks to 12 months after treatment initiation was 2.0 (95% confidence interval [CI] 1.0 – 3.1) mL/min/1.73 m 2 in the dapagliflozin group and 0.3 (95% CI -0.8 – 1.4) mL/min/1.73 m 2 in the placebo group for a between-group difference of 1.7 (95% confidence interval 0.1 – 3.3) mL/min/1.73 m ² ; p = 0.03. There were no unexpected safety signals and similar rates of adverse events, including infections, between groups. Conclusions: In heart transplant recipients, dapagliflozin, compared with placebo, improved the slope of the eGFR from 2 weeks to 12 months of treatment.