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Clinical Trial
. 2025 Oct;13(10):863-873.
doi: 10.1016/S2213-8587(25)00196-2. Epub 2025 Aug 22.

Efficacy and safety of cAMP-biased GLP-1 receptor agonist ecnoglutide versus dulaglutide in patients with type 2 diabetes and elevated glucose concentrations on metformin monotherapy (EECOH-2): a 52-week, multicentre, open-label, non-inferiority, randomised, phase 3 trial

Yang He  1 , Nianrong Mi  2 , Zhifeng Cheng  3 , Haibo Xue  4 , Jie Han  5 , Haifang Wang  6 , Huihui Wang  7 , Jun Wu  8 , Xiaoguang Shi  9 , Shuping Zhao  10 , Binhong Duan  11 , Yikun Zhu  12 , Yanqin Zhou  13 , Feng Li  14 , Xin Wang  15 , Hongwei Ling  16 , Su Wang  17 , Qingju Li  18 , Feifei Jiang  19 , Ming Yang  20 , Shaohui Bing  20 , Qing Zheng  20 , Jing Ning  20 , Mengying Guo  20 , Yue Bu  20 , Lei Guan  20 , Yao Li  20 , Liu Yang  20 , Wanjun Guo  20 , Hai Pan  20 , Xiaoying Li  21
Affiliations
Clinical Trial

Efficacy and safety of cAMP-biased GLP-1 receptor agonist ecnoglutide versus dulaglutide in patients with type 2 diabetes and elevated glucose concentrations on metformin monotherapy (EECOH-2): a 52-week, multicentre, open-label, non-inferiority, randomised, phase 3 trial

Yang He et al. Lancet Diabetes Endocrinol. 2025 Oct.

Abstract

Background: Ecnoglutide is a novel biased GLP-1 receptor agonist that preferentially activates the cAMP pathway over β-arrestin recruitment. We aimed to assess both non-inferiority and superiority of ecnoglutide versus dulaglutide, also a GLP-1 receptor agonist, in patients with type 2 diabetes.

Methods: We conducted a 52-week, open-label, active-controlled, phase 3 trial at 52 hospitals in China. Adults aged 18-75 years with a BMI of 20-35 kg/m2, a diagnosis of type 2 diabetes, and elevated glucose concentrations on metformin monotherapy were included. Participants were randomly assigned (1:1:1) to receive subcutaneous ecnoglutide (0·6 mg or 1·2 mg) or dulaglutide (1·5 mg) once weekly. The primary endpoint was mean change from baseline in HbA1c at week 32 (non-inferiority for ecnoglutide 0·6 mg and 1·2 mg, with a 0·4% non-inferiority margin; superiority for ecnoglutide 1·2 mg) and was assessed in all randomly assigned participants who received at least one dose of study treatment (full analysis set). Safety was assessed in all randomly assigned participants who received at least one dose of study drug and had at least one safety evaluation after starting treatment. This trial is registered with ClinicalTrials.gov (NCT05680129) and has ended.

Findings: Between Jan 10 and May 30, 2023, 623 participants were randomly assigned, of whom 621 comprised the full analysis set (mean age 53·9 years [SD 10·1], 347 [56%] males, 274 [44%] females, and mean HbA1c 8·40% [SD 0·78]; 68·28 mmol/mol [8·56]; 206 in the ecnoglutide 0·6 mg group, 208 in the ecnoglutide 1·2 mg group, and 207 in the dulaglutide 1·5 mg group). At week 32, mean HbA1c reductions were 1·91% (SE 0·05; -20·86 mmol/mol [0·53]) with ecnoglutide 0·6 mg, 1·89% (0·05; -20·69 mmol/mol [0·54]) with ecnoglutide 1·2 mg, and 1·65% (0·05; -18·02 mmol/mol [0·53]) with dulaglutide. Estimated treatment differences versus dulaglutide were -0·26% (95% CI -0·39 to -0·13; -2·84 mmol/mol [-4·29 to -1·38]) with ecnoglutide 0·6 mg and -0·24% (-0·38 to -0·11; -2·67 mmol/mol [-4·14 to -1·20]; p=0·0002 for superiority) with ecnoglutide 1·2 mg. HbA1c reductions were sustained to week 52. During the 52 weeks, six (3%) of 206 patients in the ecnoglutide 0·6 mg group, eight (4%) of 208 patients in the ecnoglutide 1·2 mg group, and six (3%) of 207 patients in the dulaglutide group discontinued treatment due to adverse events.

Interpretation: Once-weekly ecnoglutide 0·6 mg and 1·2 mg were non-inferior to dulaglutide 1·5 mg in reducing HbA1c in adults with type 2 diabetes and elevated glucose concentrations on metformin monotherapy. Although the 1·2 mg dose showed statistically significantly greater reductions in HbA1c from baseline to week 32 than dulaglutide 1·5 mg, the difference was not considered clinically relevant. Both doses of ecnoglutide were well tolerated. These results suggest that ecnoglutide might offer a new treatment option for type 2 diabetes.

Funding: Hangzhou Sciwind Biosciences.

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Conflict of interest statement

Declaration of interests ZC reports membership of the Standing Committee of the Asia Pacific Gout Alliance; being deputy chief of the Blood Glucose Monitoring Group, Diabetes Society, and Chinese Medical Association; committee membership of the branch of Endocrinology and Metabolism, Chinese Medical Doctor Association; membership of the Diabetes Prevention and Control Committee and the Thyroid Disease Prevention Committee, Chinese Preventive Medicine Association; and being chairman of committee for the Hyperuricemia and Gout Branch of Heilongjiang Medical Association, Diabetes Prevention and Control Branch of Heilongjiang Preventive Medicine Association, and the Endocrine Professional Group Committee of Chronic Disease Management Society of Heilongjiang Province. HW is deputy director of the Chronic Disease Management Society of Heilongjiang Province for Diabetes; vice chairperson of the Fourth Endocrinology Professional Committee of Qiqihar City; and member of the First Thyroid Disease Professional Committee of Qiqihar Anti-Cancer Association and the Standing Committee of the Diabetes Professional Committee of Qiqihar Health Education Association. JW is member of Hubei Endocrine Society, the Standing Committee of the Osteoporosis Professional Committee of the Hubei Microcirculation Society, and the Standing Committee of Wuhan Endocrine Society; and vice chairman of Endocrine and Metabolic Disease Branch of Wuhan Medical Doctor Association. SZ is member of the Standing Committee of Diabetes Professional Committee of Jilin Medical Association. YZho is deputy director of the Endocrine Society of Ping Xiang. FL is member of the Endocrinology and Metabolism Branch of the Chinese Medical Doctor Association; vice chairman of Diabetes Branch of Shandong Medical Association; member of the Endocrinology Professional Committee of Shandong Medical Association; vice chairman of the Endocrinology Branch of Shandong Medical Doctor Association; vice chairman of Thyroid Society of Shandong Preventive Medicine Association; vice chairman of Bone Metabolism and Bone Mineral Salt Branch of Shandong Medical Association; vice chairman of the Osteoporosis and Bone Mineral Salt Disease Professional Committee of Shandong Medical Doctor Association; director of the Institute of Chronic Diseases of Jining City, Shandong Province; chairman of Jining Diabetes Society; chairman of Jining Osteoporosis Society; the main person in charge of the management of chronic diseases in Jining City's “Three Highs and Six Diseases are Treated Together”. XW is a standing member of the Endocrinology Branch of Hebei Province Association of Integrated Traditional Chinese and Western Medicine, the Endocrinology Professional Committee of Hebei Geriatric Society. SW is member of the Rare Diseases Group of the Chinese Medical Association Endocrine Society, the Diabetes Group of the Chinese Medical Association Endocrine Society, the Endocrinology Branch of the Tianjin Medical Association, the Endocrine and Metabolism Branch of the Tianjin Chinese and Western Medicine Integration Association, and the Diabetes Branch of the Research Hospital; vice chairperson of the Diabetes branch of the Tianjin Society of Traditional Chinese Medicine, the Endocrine Metabolism physicians branch of the Tianjin Medical Association, the Tianjin Diabetes Prevention Association, and the Endocrinology Branch of the Tianjin Medical and Health Association; and chairperson of the Endocrinology Branch of the Tianjin Binhai New Area Medical Association. FJ, MY, SB, MG, YB, and LG are employees of Hangzhou Sciwind Biosciences. JN, YL, LY, QZ, WG, and HP are employees of and hold stocks in Hangzhou Sciwind Biosciences.

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