Abstract

Background: Type 2 diabetes mellitus is commonly associated with obesity, metabolic liver disease, and chronic low-grade inflammation. Semaglutide is known to improve glycaemic control and body weight, but its real-world associations with hepatic markers, fibrosis-related indices, and systemic inflammatory parameters remain incompletely characterized. This study evaluated changes in metabolic, hepatic, and inflammatory parameters during injectable semaglutide treatment and explored whether these changes differed according to baseline disease status. Methods: A retrospective observational study was conducted in patients with type 2 diabetes treated with injectable semaglutide 1 mg/week and followed for six months. Anthropometric, metabolic, hepatic, and inflammatory variables were collected at baseline and follow-up, including liver enzymes, the Fibrosis-4 (FIB-4) index, and the systemic immune–inflammation (SII) index. Analyses included correlation analyses and exploratory stratification according to baseline fibrosis risk and inflammatory status. Results: Semaglutide treatment was associated with significant reductions in body weight, body mass index, fasting glucose, HbA1c, and triglyceride levels. Alanine and aspartate aminotransferase levels decreased significantly, consistent with a reduction in liver enzyme abnormalities during follow-up. No significant overall changes were observed in FIB-4, an indirect fibrosis-related index, or in SII, an indirect hematological inflammatory index. However, exploratory stratified analyses suggested that patients with higher baseline FIB-4-estimated fibrosis risk or elevated SII values showed greater reductions in these indices, whereas those with low baseline risk showed no relevant changes. Conclusions: In routine clinical practice, six months of injectable semaglutide treatment was associated with favorable metabolic changes and reductions in liver transaminases in patients with type 2 diabetes mellitus. Findings related to FIB-4 and SII should be interpreted cautiously, as these are indirect indices and the baseline-dependent patterns observed were exploratory and hypothesis-generating.

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