Semaglutide-Induced Weight Loss Is the Main Determinant for the Improvement of Hepatic Biochemistry and Elastographic Repeated Measurements with FibroScan® in Patients with Type 2 Diabetes Mellitus and Metabolic Dysfunction-Associated Steatotic Liver Disease.

Abstract

Background: Semaglutide is currently being investigated for its effectiveness in metabolic dysfunction-associated steatotic liver disease (MASLD), irrespective of type 2 diabetes mellitus (T2DM) presence, even though its action on hepatic fibrosis is still debated. The aim of this study was to examine the effect of semaglutide on hepatic parameters in patients with both T2DM and MASLD in real-world clinical practice, and to further assess the significance of weight loss during treatment.

Methods: In consecutive patients with T2DM and MASLD, hepatic biochemistry and Fibrosis-4 (FIB-4) score were recorded. In participants with high FIB-4, elastographic liver stiffness measurements (LSM) and controlled attenuation parameter (CAP) were acquired with FibroScan® before and after treatment with semaglutide. For within-group comparisons, Wilcoxon signed ranked test for related samples was performed, while the role of weight loss was further investigated.

Results: A total of 111 patients were included: 31 males (27.9%), with a mean age 56.4 ± 9.7 years old, body mass index 32.7 ± 6.3 kg/m², and median glycated hemoglobin (HbA1c) 5.8% (interquartile range [IQR]: 5.6-6.2). Semaglutide (0.5-2.4 mg/week) was administered subcutaneously for a median of 12 months (IQR: 6.6-17). Thirty-three patients (29.7%) had aspartate aminotransferase and/or alanine aminotransferase above normal, and 35 (31.5%) high FIB-4 score. Apart from an overall drop in HbA1c of 5.6% (IQR: 1.6-8.6) and weight loss of 10% (IQR: 3.2-19.6), statistically significant reductions were recorded in all liver enzymes and elastographic parameters (p < 0.001). In multiple regression analysis, weight loss was found to independently predict improvements in aminotransferases and measured CAP (p < 0.001), irrespective of treatment duration and baseline FIB-4.

Conclusion: In this cohort of T2DM/MASLD patients with baseline optimal glycemic control, semaglutide-induced weight loss led to significant improvements of all hepatic parameters (biochemistry, liver stiffness, and steatosis assessed with CAP), even in MASLD patients with baseline liver enzymes within normal. This study supports the advantages of semaglutide administration in concomitant T2DM and MASLD.