Okuma Hideyuki
Department of Diabetes and Endocrinology, Graduate School of Interdisciplinary Research, Faculty of Medicine, University of Yamanashi, Yamanashi, JPN.
Cureus. 2025 May 8;17(5):e83712. doi: 10.7759/cureus.83712. eCollection 2025 May.
Tirzepatide, a glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 (GLP-1) receptor agonist, has recently been introduced in Japan; however, there are limited studies on its effectiveness in Japanese patients with type 2 diabetes diagnosed with metabolic dysfunction-associated steatotic liver disease (MASLD).
This retrospective cohort study was conducted among 54 Japanese patients (29 men and 25 women) with type 2 diabetes and MASLD to assess the impact of switching from a GLP-1 receptor agonist (GLP-1RA) to tirzepatide. Before the switch, either dulaglutide or semaglutide was used as the GLP-1RA. Clinical findings were analyzed before and six months after switching to tirzepatide. Additionally, a multiple regression analysis was performed to determine whether characteristics and test results before switching to tirzepatide could predict the weight loss and MASLD suppression six months after initiation. The fatty liver index and fibrosis-4 (FIB-4) index were utilized as MASLD indicators. High-sensitivity C-reactive protein (hsCRP) levels from residual serum were measured as an indicator of chronic inflammation.
Six months after switching to tirzepatide, significant reductions in body weight, hemoglobin A1c (HbA1c) level, fatty liver index, FIB-4 index, and hsCRP level were observed. The multiple regression analysis identified age, duration of type 2 diabetes, and HbA1c levels before the switch as significant independent predictors of weight loss rate. Also, the multiple regression analysis suggested that age before the switch may serve as a useful predictor of a decrease in fatty liver index. The effect of tirzepatide on appetite was less pronounced in the group that had used semaglutide before the switch compared with the group that had used dulaglutide; however, even in the semaglutide group, significant reductions in body weight, HbA1c levels, fatty liver index, and FIB-4 index were noted six months after the switch.
This study suggested the efficacy of switching from GLP-1RAs to tirzepatide among Japanese patients with type 2 diabetes and MASLD. Predictors of weight loss and fatty liver index reduction after switching to tirzepatide were identified. Additionally, we found that the therapeutic effect of tirzepatide can be expected even in patients who were using semaglutide before the switch.
替尔泊肽是一种葡萄糖依赖性促胰岛素多肽/胰高血糖素样肽-1（GLP-1）受体激动剂，最近已在日本上市；然而，关于其对诊断为代谢功能障碍相关脂肪性肝病（MASLD）的日本2型糖尿病患者有效性的研究有限。
本回顾性队列研究在54例患有2型糖尿病和MASLD的日本患者（29例男性和25例女性）中进行，以评估从GLP-1受体激动剂（GLP-1RA）转换为替尔泊肽的影响。在转换前，使用度拉糖肽或司美格鲁肽作为GLP-1RA。分析了转换为替尔泊肽前及转换后6个月的临床结果。此外，进行了多元回归分析，以确定转换为替尔泊肽前的特征和检测结果是否可以预测开始治疗6个月后的体重减轻和MASLD缓解情况。脂肪肝指数和纤维化-4（FIB-4）指数用作MASLD指标。测量残余血清中的高敏C反应蛋白（hsCRP）水平作为慢性炎症指标。
转换为替尔泊肽6个月后，观察到体重、糖化血红蛋白（HbA1c）水平、脂肪肝指数、FIB-4指数和hsCRP水平显著降低。多元回归分析确定转换前的年龄、2型糖尿病病程和HbA1c水平是体重减轻率的显著独立预测因素。此外，多元回归分析表明，转换前的年龄可能是脂肪肝指数降低的有用预测因素。与使用度拉糖肽的组相比，在转换前使用司美格鲁肽的组中，替尔泊肽对食欲的影响不太明显；然而，即使在司美格鲁肽组中，转换后6个月也观察到体重、HbA1c水平、脂肪肝指数和FIB-4指数显著降低。
本研究表明，在患有2型糖尿病和MASLD的日本患者中，从GLP-1RAs转换为替尔泊肽是有效的。确定了转换为替尔泊肽后体重减轻和脂肪肝指数降低的预测因素。此外，我们发现，即使是在转换前使用司美格鲁肽的患者中，也可以预期替尔泊肽的治疗效果。
