Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial.

Orforglipron, a once-daily oral nonpeptide glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated weight loss efficacy, improvements in cardiometabolic risk factors, and safety generally similar to injectable GLP-1 receptor agonists.

Orforglipron是一种每日一次口服的非肽类胰高血糖素样肽-1（GLP-1）受体激动剂，已显示出减重效果，改善心代谢风险因素，并且其安全性通常与注射型GLP-1受体激动剂相似。

Here this double-blind, placebo-controlledtrial randomized participants previously treated with tirzepatide (cohort 1: N = 205) or semaglutide (cohort 2: N = 171) during the SURMOUNT-5 study to orforglipron once daily or placebo.

在这项双盲、安慰剂对照试验中，之前接受tirzepatide治疗的参与者（队列1：N = 205）或接受semaglutide治疗的参与者（队列2：N = 171）在SURMOUNT-5研究期间被随机分配到每日一次的orforglipron或安慰剂。

Cohort 1 participants who achieved body weight plateau maintained a model-based estimate (MBE) of 74.7% (s.e.m. 4.05) of body weight reduction with orforglipron compared with an MBE of 49.2% (s.e.m. 3.92) with placebo, resulting in an estimated treatment difference of MBE 25.5% (95% confidence interval14.5 to 36.5); P < 0.001; treatment-regimen estimand) at week 52.

达到体重稳定状态的队列1参与者在使用orforglipron后，基于模型的体重减少估计值（MBE）为74.7%（标准误4.05），而使用安慰剂的MBE为49.2%（标准误3.92），治疗差异估计值为MBE 25.5%（95%置信区间14.5至36.5）；P < 0.001；治疗方案估计值）在第52周。

Cohort 2 participants who achieved body weight plateau maintained an MBE of 79.3% (s.e.m. 4.42) of body weight reduction with orforglipron compared with an MBE of 37.6% (s.e.m. 7.46) with placebo, resulting in an estimated treatment difference of MBE 41.7 (95% confidence interval24.4 to 59.0); P < 0.001; treatment-regimen estimand) at week 52.

Cohort 2的参与者在达到体重稳定期后，使用orforglipron维持了平均体重减少的79.3%（标准误4.42），而使用安慰剂的平均体重减少为37.6%（标准误7.46），估计治疗差异为MBE 41.7（95%置信区间24.4至59.0）；P < 0.001；治疗方案估计量）在第52周。

All key secondary endpoints were met.

所有关键次要终点均得到满足。

The most common adverse events were gastrointestinal effects, which were mostly mild to moderate in severity.

最常见的不良事件是胃肠道效应，大多数情况下严重程度为轻度至中度。

These data demonstrate orforglipron's potential as a globally scalable option for minimizing weight changes after injectable therapy.

这些数据展示了orforglipron作为全球可扩展选项的潜力，用于最小化注射疗法后体重变化。

Trial limitations include the absence of a comparator arm involving continued use of injectable obesity-management medications and the trial's 1-year duration.

试验的局限性包括缺乏一个涉及持续使用注射型肥胖管理药物的对照组，以及试验为期1年的时长。

ClinicalTrials.gov registration: NCT06584916 .

ClinicalTrials.gov 注册号：NCT06584916。