A practical framework for using GLP-1 RAs, SGLT2i, and MRAs with contemporary immunosuppression in kidney transplant recipients

PURPOSE OF REVIEW: Calcineurin inhibitors (CNIs) remain central to kidney-transplant (KTX) immunosuppression (IS) but contribute to nephrotoxicity and cardiometabolic (CM) complications which negatively affect patient and graft survival. This review presents a practical framework for adding glucagon-like peptide-1 receptor agonists (GLP-1 RA), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and mineralocorticoid receptor antagonists (MRAs) to established IS regimens. These agents complement individualized optimization of IS, including CNI-sparing strategies when indicated. RECENT FINDINGS: Evidence in KTX recipients remains limited, but available studies suggest that these agents may improve glycemic control, weight, blood pressure, proteinuria, and cardiorenal risk without routinely requiring changes to IS choice or dose. Whether these changes improve patient and graft survival remains unproven. GLP-1 RA related gastrointestinal effects may alter oral IS absorption, warranting continued CNI trough monitoring, particularly when significant gastrointestinal symptoms occur after initiation or dose escalation. SGLT2i require assessment of volume status, renal-function, and infection risk. MRAs may compound CNIs associated hyperkalemia and early eGFR decline, requiring close potassium and renal-function monitoring. SUMMARY: These therapies may extend cardiorenal benefits observed in nontransplant chronic kidney disease to selected KTX recipients. Their use should be individualized, introduced sequentially, and supported by monitoring of graft function, electrolytes, volume status, blood pressure, and IS exposure. Temporary withholding should follow drug-specific perioperative and sick-day guidance, particularly for SGLT2i.