Ma Jun, Hu Xiaoyan, Zhang Wencheng, Tao Mengyuan, Wang Min, Lu Weiping
Department of Endocrinology and Metabolism, The Huai'an Clinical College of Xuzhou Medical University, Huai'an, Jiangsu, 223300, China.
Department of Endocrinology and Metabolism, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu, 223300, China.
Endocrine. 2025 Jan;87(1):159-169. doi: 10.1007/s12020-024-03998-8. Epub 2024 Aug 30.
To assess and compare the therapeutic efficacy of Liraglutide, Tirzepatide, and Retatrutide in treating diabetic kidney disease (DKD) in db/db mice.
Db/db mice were administered intraperitoneal injections of Liraglutide (10 nmol/kg), Tirzepatide (10 nmol/kg), and Retatrutide (10 nmol/kg) for 10 weeks. Subsequently, we assessed the effectiveness of these three drugs in controlling blood glucose levels, reducing weight, and improving serum biochemical indicators and DKD. Additionally, we measured and compared the renal inflammation and fibrosis indexes. Meanwhile, the content of intestinal metabolite butyrate was compared to reflect the regulatory effects of these three drugs on gut microbiota.
Retatrutide demonstrated superior effectiveness in reducing weight and improving renal function in db/db mice compared to Liraglutide and Tirzepatide. Additionally, it markedly suppressed the expression of pro-inflammatory cytokines (TNF-α, caspase-1, and NLRP3) and pro-fibrotic factors (fibronectin, α-SMA, and collagen I) in the kidneys of mice. Furthermore, Retatrutide substantially enhanced liver function, reduced triglyceride levels, cholesterol levels, low-density lipoprotein cholesterol, elevated high-density lipoprotein cholesterol, and increased the content of intestinal metabolite butyrate in db/db mice when compared to the other two drugs. Unfortunately, despite its ability to lower blood glucose levels, Retatrutide did not outperform the other two drugs. In contrast, Tirzepatide exhibited better effects on lowering blood glucose, weight loss, lipid reduction, and improvement of DKD compared to Liraglutide.
Retatrutide and Tirzepatide were significantly effective in improving DKD, controlling blood glucose and body weight. Retatrutide was the most effective in improving DKD and body weight, while Tirzepatide was the most effective in controlling blood glucose. Inhibiting the expression of inflammatory factors and fibrosis mediators and regulating intestinal microbiota may be the potential mechanisms of these two drugs to delay the progression of DKD.
评估和比较利拉鲁肽、替尔泊肽和瑞他鲁肽治疗db/db小鼠糖尿病肾病（DKD）的疗效。
对db/db小鼠腹腔注射利拉鲁肽（10 nmol/kg）、替尔泊肽（10 nmol/kg）和瑞他鲁肽（10 nmol/kg），持续10周。随后，我们评估这三种药物在控制血糖水平、减轻体重以及改善血清生化指标和DKD方面的有效性。此外，我们测量并比较了肾脏炎症和纤维化指标。同时，比较肠道代谢物丁酸的含量，以反映这三种药物对肠道微生物群的调节作用。
与利拉鲁肽和替尔泊肽相比，瑞他鲁肽在减轻db/db小鼠体重和改善肾功能方面表现出更优的效果。此外，它显著抑制了小鼠肾脏中促炎细胞因子（TNF-α、半胱天冬酶-1和NLRP3）和促纤维化因子（纤连蛋白、α-平滑肌肌动蛋白和I型胶原）的表达。此外，与其他两种药物相比，瑞他鲁肽显著增强了db/db小鼠的肝功能，降低了甘油三酯水平、胆固醇水平、低密度脂蛋白胆固醇，升高了高密度脂蛋白胆固醇，并增加了肠道代谢物丁酸的含量。遗憾的是，尽管瑞他鲁肽能够降低血糖水平，但并未优于其他两种药物。相比之下，替尔泊肽在降低血糖、减轻体重、降低血脂和改善DKD方面比利拉鲁肽表现出更好的效果。
瑞他鲁肽和替尔泊肽在改善DKD、控制血糖和体重方面具有显著效果。瑞他鲁肽在改善DKD和体重方面最有效，而替尔泊肽在控制血糖方面最有效。抑制炎症因子和纤维化介质的表达以及调节肠道微生物群可能是这两种药物延缓DKD进展的潜在机制。
