SGLT2 inhibitors modify Fibrosis-4 index and mitigate the development of DKD: role of background antidiabetic drugs

Abstract Context The fibrosis-4 (FIB-4) index is a non-invasive marker for liver fibrosis and is associated with the occurrence of diabetic kidney disease (DKD). Although sodium-glucose cotransporter-2 inhibitors (SGLT2i’s) are recognized to provide cardiovascular and renal benefits, the role of SGLT2i in regulating FIB-4 index and the subsequent impact on renal events remains unclear. Objective To clarify whether FIB-4 index was associated with the development of DKD (eGFR 60mL/min/1.73m2 or new-onset macroalbuminuria) and whether the background treatment with other antidiabetic drugs modified the effects of SGLT2i on FIB-4 index and renal events. Design A retrospective cohort study. Patients A total of 136 patients with type 2 diabetes mellitus who were newly given SGLT2i for 3 years. Results Patients with high FIB-4 index (≥1.3) at baseline exhibited a higher incidence of de novo DKD, compared to those with lower FIB-4 index (1.3). This association was ameliorated in patients whose FIB-4 index was decreased during the SGLT2i treatment. Finally, among the background therapies, metformin use was associated with a decrease in FIB-4 index and a lower cumulative incidence of de novo DKD. Conclusion Elevated FIB-4 index at baseline is a potent predictor for developing DKD, and the combination therapy with SGLT2i and metformin may enhance renal protection by modulating FIB-4 index.