Background/Aim: Non-alcoholic fatty liver disease is a major cause of liver-related morbidity and mortality. Metformin is a widely used medication and may have additional benefits beyond glycemic control. Liraglutide, a novel treatment for diabetes and obesity, also has beneficial effects on non-alcoholic steatohepatitis (NASH). Metformin and liraglutide have both benefited NASH treatment. However, no study has reported the effects of combination therapy with liraglutide and metformin on NASH. Materials and Methods: We investigated the in vivo effects of metformin and liraglutide on NASH in a methionine/choline-deficient (MCD) diet-fed C57BL/6JNarl mouse model. Serum triglyceride, alanine aminotransferase and alanine aminotransferase levels were documented. Histological analysis was performed according to the NASH activity grade. Results: After treatment with liraglutide and metformin, body weight loss improved, and the liver/body weight ratio decreased. The metabolic effects and liver injury improved. Liraglutide and metformin alleviated MCD-induced hepatic steatosis and injury. Histological analysis revealed that NASH activity was reduced.
Conclusion: Our results provide evidence for the anti-NASH activity of liraglutide in combination with metformin. Liraglutide with metformin may offer the potential for a disease-modifying intervention for NASH.Non-alcoholic fatty liver disease (NAFLD) is emerging as a major cause of liver-related morbidity and mortality, with a global prevalence of 25.24% (1). It is linked to obesity, insulin resistance and metabolic syndrome, and its appearance ranges from fat accumulation to advanced fibrosis and cirrhosis (2). It is now widely recognized that NAFLD represents a continuum of liver damage, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), advanced fibrosis and cirrhosis (3, 4). The risk of developing NASH and fibrosis is significantly higher in patients with metabolic comorbidities, such as obesity, diabetes and dyslipidemia (5). While current treatment 1037