Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN
Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA.
Diabetes Care. 2020 Jun;43(6):1352-1355. doi: 10.2337/dc19-1892. Epub 2020 Apr 14.
To determine the effect of tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptors, on biomarkers of nonalcoholic steatohepatitis (NASH) and fibrosis in patients with type 2 diabetes mellitus (T2DM).
Patients with T2DM received either once weekly tirzepatide (1, 5, 10, or 15 mg), dulaglutide (1.5 mg), or placebo for 26 weeks. Changes from baseline in alanine aminotransferase (ALT), aspartate aminotransferase (AST), keratin-18 (K-18), procollagen III (Pro-C3), and adiponectin were analyzed in a modified intention-to-treat population.
Significant ( < 0.05) reductions from baseline in ALT (all groups), AST (all groups except tirzepatide 10 mg), K-18 (tirzepatide 5, 10, 15 mg), and Pro-C3 (tirzepatide 15 mg) were observed at 26 weeks. Decreases with tirzepatide were significant compared with placebo for K-18 (10 mg) and Pro-C3 (15 mg) and with dulaglutide for ALT (10, 15 mg). Adiponectin significantly increased from baseline with tirzepatide compared with placebo (10, 15 mg).
In post hoc analyses, higher tirzepatide doses significantly decreased NASH-related biomarkers and increased adiponectin in patients with T2DM.
评估葡萄糖依赖性胰岛素多肽和胰高血糖素样肽 1 受体双重激动剂替西帕肽对 2 型糖尿病（T2DM）患者非酒精性脂肪性肝炎（NASH）和纤维化生物标志物的影响。
T2DM 患者接受每周一次替西帕肽（1、5、10 或 15 mg）、度拉糖肽（1.5 mg）或安慰剂治疗 26 周。在改良意向治疗人群中分析基线时丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、角蛋白 18（K-18）、III 型前胶原（Pro-C3）和脂联素的变化。
26 周时，所有组的 ALT（均<0.05）、AST（除替西帕肽 10 mg 组外的所有组）、K-18（替西帕肽 5、10、15 mg 组）和 Pro-C3（替西帕肽 15 mg 组）均从基线显著降低。与安慰剂相比，替西帕肽治疗组的 K-18（10 mg）和 Pro-C3（15 mg）显著降低，与度拉糖肽相比，ALT（10、15 mg）显著降低。与安慰剂相比，替西帕肽治疗组的脂联素从基线显著升高（10、15 mg）。
在事后分析中，较高剂量的替西帕肽可显著降低 T2DM 患者的 NASH 相关生物标志物并增加脂联素。
