Semaglutide with Metformin Improves Liver Health and Pancreatic Function in T2DM and NAFLD: Study Reveals

"Compared to metformin alone, the combination therapy resulted in lower liver enzyme levels (ALT, AST), reduced fibrosis, better glycemic control (lower HbA1c), and enhanced beta-cell function," the researchers reported. The findings were published online in the Journal of Diabetes and its Complications on December 9, 2024.

Type 2 diabetes mellitus and non-alcoholic fatty liver disease often coexist, driven by underlying insulin resistance and systemic inflammation. There is an urgent need for effective management strategies targeting both metabolic disorders. Keeping this in mind, Rong Ren, Department of Endocrinology, Shanxi Provincial Integrated TCM And WM Hospital, Taiyuan, China, and colleagues examined the impact 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.

For this purpose, the researchers conducted a retrospective analysis of 261 patients with T2DM and NAFLD treated at our institution between January 2021 and December 2023. The participants were categorized into two groups: 127 patients received metformin alone (M group), while 134 patients received a combination of semaglutide and metformin (SAM group).

Liver inflammation and fibrosis were evaluated 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 assessed based on the Matsuda index, HbA1c, fasting glucose, and the oral disposition index (DIo).

The investigation uncovered the following findings:

Post-treatment, the SAM group exhibited significantly greater improvements in liver inflammation markers compared to the M group:

• ALT levels: 23.59 ± 5.67 U/L in SAM vs. 25.56 ± 5.46 U/L in M

• AST levels: 18.97 ± 3.94 U/L in SAM vs. 20.15 ± 3.95 U/L in M

• The SAM group demonstrated reduced fibrosis as indicated by the FIB-4 index:

• FIB-4 index: 1.05 ± 0.44 in SAM vs. 1.16 ± 0.51 in M

• Enhanced beta-cell function was observed in the SAM group:

• Matsuda index: 5.18 ± 1.09 in SAM vs. 4.84 ± 1.15 in M

• DIo (oral disposition index): 0.18 ± 0.06 in SAM vs. 0.16 ± 0.05 in M

• Glycemic control was superior in the SAM group, as reflected by reduced HbA1c levels.

The authors highlight that combining semaglutide and metformin effectively improves liver inflammation, fibrosis, beta-cell function, and insulin sensitivity in patients with T2DM and NAFLD. Their findings suggest that the beneficial effects of semaglutide combined with metformin on liver function are independent of body weight loss and glycemic control.

"These results emphasize the potential role of semaglutide as a key therapeutic option in the comprehensive management of metabolic and liver-related disorders," they concluded.

Reference:

Ren, R., Pei, Y., Kong, L., & Shi, Y. (2024). 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. Journal of Diabetes and its Complications, 108932. https://doi.org/10.1016/j.jdiacomp.2024.108932