The effect of semaglutide combined with metformin on liver inflammation and pancreatic beta-cell function in patients with type 2 diabetes and non-alcoholic fatty liver disease.

Background: Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) were often coexistent conditions driven by insulin resistance and systemic inflammation. Effective management strategies that address both metabolic disorders were urgently needed. This study investigates the effect of combining semaglutide, a glucagon-like peptide-1 receptor agonist, with metformin on liver inflammation and pancreatic beta-cell function in patients with T2DM and NAFLD.

Methods: This retrospective study analyzed 261 patients with T2DM and NAFLD treated at our institution from January 2021 to December 2023. Patients were divided into two groups: 127 received metformin alone (M group), and 134 received a combination of semaglutide and metformin (SAM group). Liver inflammation and fibrosis were assessed using alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (γ-GTP), and the FIB-4 index. Pancreatic beta-cell function and insulin sensitivity were evaluated using the Matsuda index, HbA1c, fasting glucose, and the oral disposition index (DIo).

Results: Post-treatment, the SAM group showed significantly greater improvements in liver inflammation markers (ALT: 23.59 ± 5.67 U/L in SAM vs. 25.56 ± 5.46 U/L in M; AST: 18.97 ± 3.94 U/L in SAM vs. 20.15 ± 3.95 U/L in M), reduced fibrosis (FIB-4 index: 1.05 ± 0.44 in SAM vs. 1.16 ± 0.51 in M), and enhanced beta-cell function (Matsuda index: 5.18 ± 1.09 in SAM vs. 4.84 ± 1.15 in M; DIo: 0.18 ± 0.06 in SAM vs. 0.16 ± 0.05 in M). Glycemic control, as indicated by reduced HbA1c, was also superior in the SAM group.

Conclusion: The combination of semaglutide and metformin significantly improves liver inflammation, fibrosis, and beta-cell function in patients with T2DM and NAFLD compared to metformin alone.