SGLT2 Inhibitors Modify Fibrosis-4 Index and Mitigate the Development of DKD: Role of Background Antidiabetic Drugs

The fibrosis-4 (FIB-4) index is a noninvasive marker for liver fibrosis and is associated with the occurrence of diabetic kidney disease (DKD). Although sodium-glucose cotransporter-2 inhibitors (SGLT2is) are recognized to provide cardiovascular and renal benefits, the role of SGLT2is in regulating FIB-4 index and the subsequent effect on renal events remain unclear.

This work aimed to clarify whether the FIB-4 index was associated with the development of DKD (estimated glomerular filtration rate < 60 mL/min/1.73 m² 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.

A retrospective cohort study was conducted that included 136 patients with type 2 diabetes mellitus who were newly given SGLT2is for 3 years.

Patients with a high FIB-4 index (≥1.3) at baseline exhibited a higher incidence of de novo DKD, compared to those with a 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.

Elevated FIB-4 index at baseline is a potent predictor for developing DKD, and combination therapy with SGLT2is and metformin may enhance renal protection by modulating FIB-4 index.