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

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<sub>1c</sub>) 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<sub>1c</sub> (≤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<sub>1c</sub> 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 mg. Ecnoglutide represents a potential monotherapy option for T2DM. This trial was registered at clinicaltrials.gov with the registration number NCT05680155.

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Journal
Nature Communications
Published
2026-01-07
DOI
https://doi.org/10.1038/s41467-025-68165-7
Primary Topic
Diabetes Treatment and Management
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article
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article

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

Ming Yang, Pang Shuguang, Xiaoxia Shi, Hongcheng Ding et al.
Nature Communications
Diabetes Treatment and Management
article

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

Ming Yang, Pang Shuguang, Xiaoxia Shi, Hongcheng Ding, Hongbo Pan, Guoyu Tong, BINHONG WEN, Weimin Wang, Bimin Shi, YIBING LU, XINGQUAN LIU, Qing Zheng, Susan H. Xu, CHENGXIA JIANG, SHAOHUI BING, Yue Bu, D H Huang, Xianghua Zhang, Dalong Zhu, Yao Li, Liujun Fu, Mengying Guo, Wanjun Guo, Haibo Xue, Jing Ning, Feifei Jiang, Lei Guan, Tianrong Pan, Jie Han, Jianhua Ma, Yang Liu, Kun Wang, Xin Zheng, Liu Yang
article en

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<sub>1c</sub>) 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<sub>1c</sub> (≤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<sub>1c</sub> 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 mg. Ecnoglutide represents a potential monotherapy option for T2DM. This trial was registered at clinicaltrials.gov with the registration number NCT05680155.

Nature CommunicationsVol. 17(1)
Hunan Institute of Science and Technology (CN), Hubei University of Medicine (CN), National Federation of the Blind (US), Binzhou Medical University (CN), Shandong University of Aeronautics (CN), Harbin Medical University (CN), Anhui Medical University (CN), Soochow University (CN), Daqing City People's Hospital (CN), National Clinical Research Center for Digestive Diseases (CN), Shanghai University of Traditional Chinese Medicine (CN), ENN (China) (CN), Liaoning Provincial People's Hospital (CN), Jinan Central Hospital (CN), Nanjing Drum Tower Hospital (CN), BD Biosciences (United States) (US), Beijing Hospital (CN), Yueyang Second People's Hospital (CN), Yueyang Hospital (CN), First Affiliated Hospital of Henan University of Science and Technology (CN), Nanyang Medical College (CN), Second Affiliated Hospital of Nanjing Medical University (CN), Second Affiliated Hospital of Anhui Medical University (CN), First Affiliated Hospital of Soochow University (CN), Nanjing Jiangning Hospital (CN), Second People’s Hospital of Yibin (CN), Shandong First Medical University (CN), Third Hospital of Changsha (CN), Nanjing Medical University (CN)
American Diabetes Association
Good health and well-being
Openalex Percentile: Top 96%
Diabetes Treatment and Management
DOIOpen Access PDFOpenAlex
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