Mimura Hanaka, Oura Tomonori, Chin Rina, Takeuchi Masakazu, Fujihara Kazuya, Sone Hirohito
Japan Drug Development and Medical Affairs, Eli Lilly Japan K.K., Kobe, Japan.
Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine, Niigata, Japan.
J Diabetes Investig. 2025 May;16(5):807-816. doi: 10.1111/jdi.14395. Epub 2025 Feb 1.
AIMS/INTRODUCTION: In the SURPASS J-mono trial, tirzepatide demonstrated significant improvements in bodyweight and several metabolic parameters in Japanese participants with type 2 diabetes. This post hoc analysis evaluated the potential relationships between weight loss and metabolic improvements in SURPASS J-mono.
Metabolic parameter data from tirzepatide-treated participants were analyzed by weight loss subgroups and compared to dulaglutide 0.75 mg. Correlations between changes from baseline to week 52 in weight loss and each metabolic parameter were assessed; Pearson correlation coefficients were derived. Mediation analyses were conducted to evaluate weight loss-associated and -unassociated effects of tirzepatide vs dulaglutide 0.75 mg.
This analysis included 548 participants (tirzepatide: n = 411, dulaglutide: n = 137). Weight loss subgroups showed greater improvement in metabolic parameters with greater bodyweight loss. Significant (P < 0.05) but weak correlations between changes in bodyweight and triglycerides (r = 0.18-0.25), high-density lipoprotein cholesterol (r = -0.37 to -0.29), and systolic blood pressure (r = 0.19-0.41) were observed across treatment groups; in diastolic blood pressure in the tirzepatide 5-mg (r = 0.28), pooled tirzepatide (r = 0.20), and dulaglutide 0.75-mg (r = 0.23) groups; and in fasting serum glucose in the dulaglutide 0.75-mg (r = 0.18) and pooled tirzepatide (r = 0.13) groups. Weight loss was associated with treatment differences between tirzepatide and dulaglutide 0.75 mg to varying degrees across metabolic parameters, with improvements in fasting serum glucose having the lowest association with weight loss (36.6%-43.5%).
In this post hoc analysis, non-glycemic and glycemic parameter improvements appeared differentially associated with weight loss, suggesting both weight loss-associated and -unassociated effects of tirzepatide.
目的/引言：在SURPASS J-单药试验中，替尔泊肽在日本2型糖尿病参与者的体重和多个代谢参数方面显示出显著改善。这项事后分析评估了SURPASS J-单药试验中体重减轻与代谢改善之间的潜在关系。
对接受替尔泊肽治疗的参与者的代谢参数数据按体重减轻亚组进行分析，并与度拉糖肽0.75mg进行比较。评估了从基线到第52周体重减轻与每个代谢参数变化之间的相关性；得出了Pearson相关系数。进行中介分析以评估替尔泊肽与度拉糖肽0.75mg的体重减轻相关和不相关效应。
该分析纳入了548名参与者（替尔泊肽组：n = 411，度拉糖肽组：n = 137）。体重减轻亚组显示，体重减轻越多，代谢参数改善越大。在各治疗组中，体重变化与甘油三酯（r = 0.18 - 0.25）、高密度脂蛋白胆固醇（r = -0.37至-0.29）和收缩压（r = 0.19 - 0.41）之间存在显著（P < 0.05）但较弱的相关性；在替尔泊肽5mg组（r = 0.28）、替尔泊肽合并组（r = 0.20）和度拉糖肽0.75mg组（r = 0.23）的舒张压中；以及在度拉糖肽0.75mg组（r = 0.18）和替尔泊肽合并组（r = 0.13）的空腹血清葡萄糖中。在不同代谢参数方面，体重减轻与替尔泊肽和度拉糖肽0.75mg之间的治疗差异存在不同程度的关联，空腹血清葡萄糖改善与体重减轻的关联最低（36.6% - 43.5%）。
在这项事后分析中，非血糖和血糖参数的改善与体重减轻的关联似乎不同，这表明替尔泊肽具有体重减轻相关和不相关的效应。
