Mazdutide对比安慰剂在中国2型糖尿病患者中的疗效研究，这一成果由信达生物制药集团钱镭团队经过不懈努力而取得。相关论文发表在2025年12月17日出版的《自然》杂志上。

在这里，该课题组评估了双胰高血糖素受体(GCGR)/胰高血糖素样肽-1受体（GLP-1R）激动剂马都肽单药治疗与安慰剂治疗在单独饮食和运动控制不足的中国成人T2D患者中的疗效和安全性。在这项3期试验中，320名参与者（平均HbA1c为8.24%，BMI为28.2 kg/m²，糖尿病持续时间为1.9年）被随机分为1:1组，接受每周一次皮下注射4 mg、6 mg或安慰剂，持续24周，随后进行24周的延长治疗。在第24周，与安慰剂相比，马都肽显著降低HbA_1c（主要终点）：马都肽4 mg组降低-1.57%，马都肽6 mg组降低-2.15%，而安慰剂组降低-0.14%，治疗差异为-1.43%和-2.02%（均p <0.0001）。第24周体重显著减轻，分别为-5.61% （4 mg）和-7.81% (6 mg)，而安慰剂组为-1.26% （p<均为0.0001）。此外，与安慰剂相比，服用马都肽的参与者达到临床相关的HbA_1c目标（<7.0%）、体重减轻目标（≥5%）和复合终点（HbA_1c <7.0%和体重减轻≥5%）的人数明显更多（p <0.0001）。最常见的不良事件-腹泻，食欲下降和恶心-与GLP-1R激动剂一致。这些结果表明，马都肽单药治疗是一种有效的干预措施，可在该人群中提供具有临床意义的血糖控制和体重减轻，同时具有良好的安全性。

据介绍，尽管2型糖尿病（T2D）的治疗取得了进展，但在有效控制高血糖的同时解决合并症代谢紊乱的治疗方面仍存在未满足的需求。

附：英文原文

Title: Mazdutide versus placebo in Chinese adults with type 2 diabetes

Author: Zhu, Dalong, Zhao, Jiajun, Cai, Hanqing, Chu, Xuan, Xiu, Shuangling, Song, Chengwei, Cheng, Zhifeng, Cao, Hongyi, Jiang, Hongwei, Zhang, Lili, Wang, Haifang, Shi, Bimin, Li, Yanbing, Liu, Ming, Feng, Bo, Xue, Fengtai, Deng, Huan, Li, Haoyu, Li, Li, Li, Yue, Ma, Qingyang, Qian, Lei

Issue&Volume: 2025-12-17

Abstract: Despite advances in type 2 diabetes (T2D) management, unmet needs remain for therapies that effectively control hyperglycaemia while addressing the comorbid metabolic disorders1, 2. Here we assessed the efficacy and safety of the dual glucagon receptor (GCGR)/glucagon-like peptide-1 receptor (GLP-1R) agonist mazdutide monotherapy versus placebo in Chinese adults with T2D inadequately controlled with diet and exercise alone. In this phase 3 trial, 320 participants (mean HbA1c of 8.24%, BMI of 28.2 kg/m2, and diabetes duration of 1.9 years) were randomised 1:1:1 to receive weekly subcutaneous injections of mazdutide 4 mg, 6 mg, or placebo for 24 weeks, followed by a 24-week extended mazdutide treatment. At week 24, mazdutide significantly reduced HbA1c versus placebo (primary endpoint): -1.57% with mazdutide 4 mg and -2.15% with mazdutide 6 mg, versus -0.14% with placebo, with treatment differences of -1.43% and -2.02% (both p <0.0001). Significant weight loss at week 24 occurred with -5.61% (4 mg) and -7.81% (6 mg) versus -1.26% (placebo) (both p<0.0001). Additionally, significantly more participants with mazdutide achieved clinically relevant HbA1c target (<7.0%), weight loss goal (≥5%), and composite endpoints (HbA1c <7.0% and weight loss ≥5%) versus placebo (all p <0.0001). The most common adverse events—diarrhoea, decreased appetite, and nausea—were consistent with GLP-1R agonists. These results establish mazdutide monotherapy as an effective intervention providing clinically meaningful glycaemic control and weight reduction alongside a favourable safety profile in this population.

DOI: 10.1038/s41586-025-10026-w

Source: https://www.nature.com/articles/s41586-025-10026-w