Sodium-Glucose Cotransporter 2 Inhibitors' Mechanism of Action and Use in Kidney Transplantation Recipients: Extended Review and Update

Abstract

Five sodium-glucose cotransporters (SGLTs) protein family members are important for regulating blood glucose levels. The essential cotransporters for glucose reabsorption by proximal convoluted tubule are SGLT1 and 2. The newest recommendations advocate GLT2 inhibitors as first-line treatment for type 2 diabetes (T2D) with and without chronic kidney disease (CKD), improving CKD and cardiovascular outcomes.SGLT2 inhibitors enhance kidney transplant patients' life quality, delay CKD progression, have renoprotective effects, and reduce cardiovascular disease in CKD patients, despite minimal published evidence on the usage of SGLT2 inhibitors in kidney transplantation recipients (KTxRs) with T2D or new-onset T2D. They preserve and improve renal function and cardiovascular outcomes in KTxRs. SGLT2 inhibitors' safety issues have prevented KTxRs from participating in major randomized studies, leaving doctors and patients unsure whether these extraordinary drugs outweigh the risks.This extended review analyzes the established mechanisms through which SGLT2 inhibitors exert their positive effects, evaluate the potential advantages and drawbacks of these agents in KTx, and examine the current research findings on using SGLT2 inhibitors in KTxRs. Additionally, potential avenues for future research will be suggested. Different phrases were used to search for recent original and review articles published between January 2020 and November 2023 in PubMed, Google Scholar, Scopus, EMBASE, and Google to achieve the review objectives.