Empagliflozin and its impact on hepatic and metabolic outcomes in patients with type 2 diabetes and NAFLD: a systematic review and meta-analysis.

BACKGROUND

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly nonalcoholic fatty liver disease (NAFLD), often coexists with type 2 diabetes mellitus (T2DM) due to shared metabolic pathways such as insulin resistance. Empagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, may provide hepatic and metabolic benefits. This study evaluated its effects on liver fat, enzymes, fibrosis, metabolic parameters, and inflammation in T2DM with MASLD.

METHODS

A systematic review and meta-analysis of randomized controlled trials (RCTs) was performed according to PRISMA guidelines. Primary outcomes included liver fat content, enzymes, and fibrosis markers. Secondary outcomes were metabolic and inflammatory parameters.

RESULTS

Eleven RCTs (n = 3077) were included. Empagliflozin significantly reduced liver fat (MD = -3.11%; 95% CI: -4.12 to -2.11; p < 0.00001) and liver stiffness (MD = -0.43 kPa; p = 0.003), but had no significant effect on AST (-0.27 IU/L; p = 0.89) or GGT (-9.25 IU/L; p = 0.14). It significantly lowered HbA1c (-0.54%; p < 0.0001), fasting glucose (-20.89 mg/dL; p < 0.0001), weight (-2.04 kg; p < 0.0001), and waist circumference (-3.47 cm; p < 0.0001), with a nonsignificant reduction in BMI (-0.77 kg/m²; p = 0.09).Uric acid decreased (-0.41 mg/dL; p < 0.00001), but IL-6 and fibrosis scores (FIB-4, NFS) remained unchanged.

CONCLUSION

Empagliflozin improves liver fat, stiffness, glycemic control, body weight, and uric acid in T2DM with MASLD, but its effects on fibrosis and inflammation remain uncertain. Larger, long-term histologic trials are needed to confirm these outcomes.