Safety and efficacy of sodium-glucose cotransporter 2 inhibitors in post-heart transplant patients: A multi-center retrospective cohort study

Background: Despite compelling mechanistic and clinical data supporting the use of sodium glucose cotransporter 2 inhibitors (SGLT2i) in heart failure, chronic kidney disease (CKD), and type 2 diabetes (T2DM), the safety and efficacy of SGLT2i in patients with prior orthotopic heart transplant (OHT) patients remain underexplored, potentially due to concerns surrounding infection risk and kidney injury. Methods: This was a retrospective cohort study of patients receiving an SGLT2i following OHT at 7 large transplant centers between July 2016 and December 2023 to assess safety and tolerability. Key outcomes of interest included hospitalization attributed to SGLT2i use, genital/urinary tract (GU) infection, and acute kidney injury (AKI), as well as discontinuation of SGLT2i. Results: Overall, 141 patients across 7 transplant centers were included in this cohort analysis. Patients had a median age of 61, and the median time from transplant was 5.3 years. Rates of hospitalization related to SGLT2i were low, occurring in 1.4% of the study population (2/141) at a rate of 0.007 events/person-year. GU infections occurred in 9.93% (14/141) of patients, and AKI within 30 days was observed in 20.59% (21/102 patients who had a complete dataset available for analysis). At the end of the observation period, 68.1% of patients remained on an SGLT2i, and 31.9% had discontinued their SGLT2i: 15.6% of patients discontinued their SGLT2i for medical reasons, most commonly AKI or GU infection. Conclusion: Our results suggest that though discontinuation of SGLT2i use was high in patients post-OHT, the overall safety profile of the drug class was reassuring, with a low observed risk of hospitalization, kidney failure, or GU infection. Future larger prospective studies are needed to more fully elucidate the impact of SGLT2i on long-term outcomes in patients following OHT.