Department of Pharmacy, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, R.O.C.
Graduate Institute of Clinical Pharmacy, College of Medicine, Tzu Chi University, Hualien, Taiwan, R.O.C.
In Vivo. 2023 May-Jun;37(3):1037-1046. doi: 10.21873/invivo.13178.
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.
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.
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.
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.
背景/目的:非酒精性脂肪性肝病是导致肝相关发病率和死亡率的主要原因。二甲双胍是一种广泛应用的药物,除了控制血糖外,可能还有其他益处。利拉鲁肽是一种新型的糖尿病和肥胖症治疗药物,对非酒精性脂肪性肝炎(NASH)也有有益的影响。二甲双胍和利拉鲁肽都有益于 NASH 的治疗。然而,尚无研究报道利拉鲁肽和二甲双胍联合治疗 NASH 的效果。
我们在蛋氨酸/胆碱缺乏(MCD)饮食喂养的 C57BL/6JNarl 小鼠模型中研究了二甲双胍和利拉鲁肽对 NASH 的体内作用。记录血清甘油三酯、丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平。根据 NASH 活动评分进行组织学分析。
用利拉鲁肽和二甲双胍治疗后,体重减轻,肝/体重比降低。代谢作用和肝损伤得到改善。利拉鲁肽和二甲双胍减轻了 MCD 诱导的肝脂肪变性和损伤。组织学分析显示 NASH 活性降低。
我们的结果为利拉鲁肽联合二甲双胍的抗 NASH 活性提供了证据。利拉鲁肽联合二甲双胍可能为 NASH 的疾病修饰干预提供了潜力。