Adding Semaglutide to SGLT2 Inhibitors Reduces Liver Enzymes in Patients with Type 2 Diabetes Complicated by Metabolic Dysfunction Associated Steatotic Liver Disease: A Retrospective Observational Study

Objective To investigate the additive effects of semaglutide on liver function indicators in patients with type 2 diabetes mellitus (T2DM) complicated by metabolic dysfunction-associated steatotic liver disease (MASLD), who received sodium-glucose cotransporter 2 inhibitors (SGLT2-Is). Methods Liver function indicators at baseline were compared with those 6 months after the initiation of semaglutide. Patients Forty-seven patients (mean age, 56.2±10.4 years; 74.5% men) with T2DM complicated by MASLD who were prescribed SGLT2-Is continuously for at least 12 months were retrospectively selected. Results Six months of semaglutide treatment significantly decreased body weight (BW; 80.9±16.4 kg to 77.3±17.0 kg, p<0.001), body mass index (BMI; 28.9±4.5 kg/m² to 27.7±4.6 kg/m², p<0.001), and the levels of glycated hemoglobin (HbA1c; 7.4% ±0.7% to 6.9% ±0.7%, p<0.001), aspartate aminotransferase (AST; 30.4±15.9 U/L to 26.3±12.5 U/L, p=0.014), alanine aminotransferase (ALT; 42.4±28.7 U/L to 35.7±22.8 U/L, p=0.022), and gamma-glutamyl transpeptidase (γ-GTP; 46.5±36.8 U/L to 38.0±30.0 U/L, p=0.001). The fibrosis-4 index, an indicator of liver fibrosis, did not improve. Changes in ALT levels were significantly correlated with changes in metabolic parameters, including BW (P=0.004), BMI (p=0.004), HbA1c (p=0.005), and triglycerides (p=0.011). Conclusion The addition of semaglutide to SGLT2-Is reduced liver enzyme levels in patients with T2DM complicated with MASLD. Future randomized controlled trials are needed to investigate the additive effects of semaglutide on MASLD in patients with T2DM receiving SGLT2-Is.