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替尔泊肽实现持续体重减轻并控制血糖的时间:SURPASS临床试验项目的事后分析

Time spent in glycaemic control with sustained body weight reduction with tirzepatide: A post hoc analysis of the SURPASS clinical trial programme.

作者信息

Bergman Brandon K, Rosenstock Julio, Garvey W Timothy, Batterham Rachel L, Chen Yanyun, Liu Minzhi, Sharma Palash, Karanikas Chrisanthi A, Thieu Vivian T

机构信息

Eli Lilly and Company, Indianapolis, Indiana, USA.

Velocity Clinical Research at Medical City, Dallas, Texas, USA.

出版信息

Diabetes Obes Metab. 2025 Jun;27(6):3223-3232. doi: 10.1111/dom.16337. Epub 2025 Mar 13.

Abstract

AIMS

This participant-level exploratory analysis assessed the continuous time spent in glycaemic control and/or with sustained weight reductions with tirzepatide treatment in participants with type 2 diabetes (T2D) from the SURPASS programme.

MATERIALS AND METHODS

Participants (N = 6246) from SURPASS 1-5 were randomized to once weekly tirzepatide (5, 10 or 15 mg) or comparator (once weekly placebo, once weekly semaglutide 1 mg, insulin degludec or insulin glargine). Continuous time spent with HbA1c < 7.0% (53 mmol/mol), ≤6.5% (48 mmol/mol) and ≥5% body weight reduction and combined HbA1c ≤ 6.5% (48 mmol/mol) with a ≥5% body weight reduction were assessed through 40 weeks (SURPASS-1, -2, and -5) or 52 weeks (SURPASS-3 and -4). The non-parametric Wilcoxon rank sum test was used to compare the median duration of continuous time spent in control, and logistic regression was used to analyse the proportion of participants achieving glycaemic control and body weight reduction at any time points or at the end of the primary study period.

RESULTS

Median time spent with HbA1c < 7.0% (53 mmol/mol) was 80% (tirzepatide) versus 70% (semaglutide) and 0% (placebo) of the treatment duration in 40-week studies, and 77%-85% (tirzepatide) versus 62% (insulin degludec) and 23% (insulin glargine) of the treatment duration in 52-week studies (p < 0.001). Time spent with HbA1c < 7.0% (53 mmol/mol) was generally similar across all tirzepatide doses in each study. Dose-dependent increases in time spent with ≥5% body weight reduction were observed with tirzepatide (median time spent: 20%-77% with tirzepatide versus 25% with semaglutide 1 mg) (p < 0.001). Tirzepatide-treated participants experienced longer time spent with HbA1c ≤ 6.5% (48 mmol/mol) and ≥5% body weight reduction versus semaglutide (median: 35%-60% vs. 7%) (p < 0.001).

CONCLUSIONS

In this post hoc analysis, people with T2D experienced substantially longer continuous time in glycaemic control and more sustained body weight reductions with tirzepatide versus placebo and active comparators.

摘要

目的

这项基于参与者层面的探索性分析评估了来自SURPASS项目的2型糖尿病(T2D)患者使用替尔泊肽治疗后血糖得到控制和/或体重持续减轻的连续时间。

材料与方法

SURPASS 1 - 5研究中的参与者(N = 6246)被随机分配至每周一次的替尔泊肽(5、10或15毫克)组或对照药物组(每周一次安慰剂、每周一次司美格鲁肽1毫克、德谷胰岛素或甘精胰岛素)。通过40周(SURPASS - 1、 - 2和 - 5)或52周(SURPASS - 3和 - 4)评估糖化血红蛋白(HbA1c)< 7.0%(53 mmol/mol)、≤6.5%(48 mmol/mol)以及体重减轻≥5%和糖化血红蛋白≤6.5%(48 mmol/mol)且体重减轻≥5%的连续时间。采用非参数Wilcoxon秩和检验比较血糖控制的连续时间中位数,并使用逻辑回归分析在任何时间点或主要研究期结束时实现血糖控制和体重减轻的参与者比例。

结果

在40周的研究中,HbA1c < 7.0%(53 mmol/mol)的中位时间占治疗持续时间的比例,替尔泊肽组为80%,司美格鲁肽组为70%,安慰剂组为0%;在52周的研究中,替尔泊肽组为77% - 85%,德谷胰岛素组为62%;甘精胰岛素组为23%(p < 0.001)。在每项研究中各替尔泊肽剂量组间HbA1c < 7.0%(53 mmol/mol)所花费的时间总体相似。观察到替尔泊肽使体重减轻≥5%的时间呈剂量依赖性增加(中位时间:替尔泊肽组为20% - 77%,司美格鲁肽1毫克组为25%)(p < 0.001)。与司美格鲁肽相比,接受替尔泊肽治疗的参与者糖化血红蛋白≤6.5%(48 mmol/mol)且体重减轻≥5%的时间更长(中位数:35% - 60%对7%)(p < 0.001)。

结论

在这项事后分析中,与安慰剂及活性对照药物相比,2型糖尿病患者使用替尔泊肽后血糖得到控制的连续时间显著更长,体重减轻更持久。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1b2/12046485/f7a2e34d3788/DOM-27-3223-g005.jpg

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