Dose-dependent acute effects of liraglutide on liver function and metabolic parameters in healthy rats

Year 2025, Volume: 16 Issue: 56, 193 - 204, 16.12.2025

Aytaç Gül , Hüseyin Özkan , Mehmet Güvenç , Tuğba Çalışır

https://doi.org/10.17944/interdiscip.1782720

Abstract

Objective: Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist widely used in type 2 diabetes mellitus and has well-documented metabolic and cardiovascular benefits. However, its acute hepatic and metabolic effects in healthy conditions remain poorly understood. This study aimed to investigate the dose-dependent acute effects of liraglutide on hepatic and metabolic biochemical parameters in rats.
Methods: Twenty-eight female Wistar albino rats were randomly assigned to four groups: control (PBS), and low (50 μg/kg), medium (100 μg/kg), or high dose (300 μg/kg) liraglutide. After 12 hours of fasting, a single subcutaneous injection was administered, and blood samples were collected 6 hours later for biochemical analysis of hepatic and metabolic parameters. Group differences were assessed by one-way ANOVA with Tukey’s post hoc test, and correlation analyses were performed within each group.
Results: Significant dose-dependent effects of liraglutide on hepatic enzymes and metabolic parameters were detected. Also, significant group effects were observed for alanine aminotransferase (ALT) (p = 0.034), aspartate aminotransferase (AST) (p = 0.026), glucose (p < 0.001), triglycerides (p = 0.021), and albumin (p = 0.020). ALT was elevated at low dose but not at higher doses. AST was reduced in medium- and high-dose groups. Glucose increased progressively across all treated groups, while triglycerides decreased, and albumin increased at high dose. Alkaline phosphatase (ALP), total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), lactate dehydrogenase (LDH), and total protein showed similar levels (p > 0.05).
Conclusion: Liraglutide acutely modulates selected hepatic and metabolic parameters in a dose-dependent manner. These results provide insight into short-term hepatic profile of liraglutide and inform its safety assessment under normal liver conditions.

Keywords

Liraglutide , acute hepatic effects , dose-dependent response , biochemical parameters

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