Sodium glucose cotransporter 2 inhibitor use after heart transplant: Current knowledge and potential applications.

Raven LM, Brinker L, Sideris K, Muir CA, Carter S, Beddhu S, Macdonald PS, Stehlik J. Sodium glucose cotransporter 2 inhibitor use after heart transplant: Current knowledge and potential applications. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2025 Nov 1; 25(11):2303-2312, DOI: 10.1016/j.ajt.2025.08.013.

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Abstract:

Heart transplant (HTx) markedly improves survival and quality of life in patients with stage D heart failure. However, long-term survival post-HTx is limited by increased risk and progression of cardiovascular disease, chronic kidney disease, and metabolic disease. There is a lack of proven mitigating treatments for these morbidities, and transplant recipients are frequently excluded from clinical trials of novel agents, which could be of benefit in this population. Sodium glucose cotransporter 2 inhibitors (SGLT2i), initially a treatment for type 2 diabetes, are now established treatments for heart failure or chronic kidney disease, with or without type 2 diabetes. There are strong mechanistic reasons that suggest HTx recipients should derive specific benefits from SGLT2i. However, prospective data to confirm these hypotheses in transplant recipient populations are limited. In this review, we present mechanisms through which SGLT2i may benefit HTx recipients, including renoprotective, glycemic, vascular, anti-inflammatory, and erythropoietic effects. We present a summary of experimental studies of SGLT2i in reversal of calcineurin inhibitor-associated kidney and pancreatic injury, and retrospective studies of SGLT2i in HTx recipients demonstrating improvement in glycaemia, weight, and renal function. Prospective trials of SGLT2i in HTx recipients are required, and the currently registered trials are highlighted.