Could the administration of SGLT2i agents serve as a viable prophylactic approach against CNI-induced toxicities?

Calcineurin inhibitors (CNIs) are a class of immunosuppressants utilized to manage autoimmune disorders and to prevent rejection in solid organ transplantations. CNIs are associated with various side effects, including new-onset diabetes, dyslipidemia, hypertension, nephrotoxicity, cardiovascular risks, electrolyte imbalances, and neurotoxicity. Preventing these complications is crucial for improving the patients’ quality of life and survival. One strategy widely used to prevent these side effects is to employ a multi-drug immunosuppressive regimen to eliminate or reduce the CNI dose. However, the efficacy of this strategy is relatively low and there is a possibility of causing side effects by other drugs. As a result, novel approaches are needed to prevent or manage complications related to CNIs. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are a type of antidiabetic medication that has gained increased usage. Preliminary clinical trials suggest that administering these drugs to diabetic patients is linked to improved renal and cardiovascular outcomes. Their prescription has also been recommended for non-diabetic patients with chronic kidney disease (CKD) and heart failure (HF). Our hypothesis is that SGLT2is can prevent or delay metabolic and vascular complications associated with CNIs due to their anti-diabetic, anti-hypertensive, anti-inflammatory, anti-fibrotic, antioxidant, and anti-apoptotic effects, as well as their ability to improve endothelial function. Additionally, SGLT2is have the potential to reverse electrolyte imbalances and neurological disorders caused by CNIs based on their effects on tubular function and neuroprotective properties. If the hypothesis were to be confirmed, the implications for science would be the prolongation of lifespan in patients treated with CNIs by targeting several side effects mechanisms with one drug.