FIB-4 Trajectories and Predictors of Fibrosis Response in Type 2 Diabetes Treated with SGLT2 Inhibitors: A Propensity-Matched 12-Month Study

Abstract Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have demonstrated favorable effects on metabolic parameters, yet their impact on liver fibrosis indices such as the Fibrosis-4 (FIB-4) score remains underexplored. Understanding the comparative efficacy of empagliflozin and dapagliflozin in modulating hepatic and metabolic markers could guide therapeutic strategies in patients with type 2 diabetes mellitus (T2DM). Methods: This study included patients with T2DM who were initiated on empagliflozin or dapagliflozin and followed for 12 months. Clinical and laboratory parameters were assessed at baseline and 12 months, including weight, HbA1c, lipid profile, ALT, AST, and FIB-4 score. Propensity score matching was employed to identify responders (≥20% reduction in FIB-4) and non-responders. Receiver operating characteristic (ROC) analysis was performed to evaluate predictive markers for FIB-4 improvement. Results: A total of 200 patients were analyzed. Both empagliflozin and dapagliflozin groups demonstrated significant reductions in BMI, FBG, HbA1c, and FIB-4 scores (p < 0.001 for all). Between-group comparisons revealed no statistically significant differences in ΔBMI, ΔHbA1c, ΔAST, or ΔFIB-4. Among responders, the baseline FIB-4 score was significantly lower (1.48±0.52 vs. 1.80±0.42; p = 0.0445). ROC analysis identified ΔAST ≥7 U/L as the strongest predictor of FIB-4 response (AUC = 0.875, sensitivity = 83%, specificity = 83%). Conclusion: Both SGLT2 inhibitors significantly improved metabolic and hepatic parameters in patients with T2DM. The magnitude of AST reduction emerged as a robust predictor of FIB-4 improvement, underscoring its potential role in monitoring hepatic response to treatment.