Efficacy and safety of cAMP signalling-biased GLP-1 analogue ecnoglutide monotherapy versus placebo in patients with type 2 diabetes (EECOH-1): a multi-centre, randomised, double-blind, placebo-controlled, phase 3 trial

作者：Dalong Zhu, Weimin Wang, Guoyu Tong, Jianhua Ma, BINHONG WEN, Xin Zheng, Bimin Shi, Pang Shuguang, Kun Wang, Xiaoxia Shi, Xianghua Zhang, Liujun Fu, Yang Liu, YIBING LU, D H Huang, CHENGXIA JIANG, Tianrong Pan, Haibo Xue, Jie Han, Hongcheng Ding, SHAOHUI BING, Feifei Jiang, Qing Zheng, Ming Yang, Lei Guan, XINGQUAN LIU, Jing Ning, Yue Bu, Mengying Guo, Liu Yang, Wanjun Guo, Yao Li, Susan H. Xu, Hongbo Pan · 发表于：Nature Communications · 年份：2026 · DOI：10.1038/s41467-025-68165-7 · 被引用次数：5 · 研究领域：Diabetes Treatment and Management、Pharmacology and Obesity Treatment、Pancreatic function and diabetes

Abstract Ecnoglutide is a cAMP-biased GLP-1 analogue developed for the treatment of type 2 diabetes mellitus (T2DM) and obesity. We conducted a randomised, double-blind, placebo-controlled, phase 3 trial to evaluate the efficacy and safety of ecnoglutide in adults with T2DM inadequately controlled with diet and exercise alone or with a single oral hypoglycaemic agent. The primary endpoint was change in glycated haemoglobin (HbA 1c ) from baseline at week 24. Between 29 December 2022 and 12 June 2024, 211 participants from 32 medical centres in China were randomised (2:2:1:1) to receive double-blind, once-weekly ecnoglutide (0.6 mg [n = 69] or 1.2 mg [n = 71]) or volume-matched placebo (0.6 mg [n = 36] or 1.2 mg [n = 35]) for 24 weeks. The randomisation, stratified by baseline HbA 1c (≤8.5% or >8.5%), was conducted via an interactive web response system. Ecnoglutide and placebo were identical in appearance to achieve masking. The trial was completed. All randomised participants received ≥1 dose of the assigned treatment and thus were included for analyses. At week 24, the least squares mean changes from baseline in HbA 1c were −1.96% (95% CI −2.18 to −1.73) with ecnoglutide 0.6 mg and −2.43% (95% CI −2.65 to −2.20) with ecnoglutide 1.2 mg versus −0.87% (−1.09 to −0.65) with placebo. The estimated treatment differences versus placebo were −1.09% (95% CI −1.40 to −0.77; p = 0.0003) with ecnoglutide 0.6 mg and −1.56% (95% CI −1.87 to −1.24; p < 0.0001) with ecnoglutide 1.2 ...