Efsubaglutide alfa added to metformin improves glycaemia with β-cell functional responses in type 2 diabetes: a randomised, double-blind, placebo-controlled, two-stage adaptive phase 2b/3 trial (SUPER 2)
Efsubaglutide alfa, a long-acting humanised GLP-1 receptor agonist, was evaluated as add-on therapy to metformin in adults with type 2 diabetes. In an operationally seamless adaptive phase 2b/3, randomised, double-blind, placebo-controlled trial, phase 2b randomised participants 1:1:1 to Efsubaglutide 1 mg, 3 mg, or placebo for 12 weeks; based on phase 2b efficacy and safety, an independent committee selected 3 mg as the recommended phase 3 dose. Phase 3 randomised new participants 1:1 to Efsubaglutide 3 mg or placebo for 24-week double-blind treatment, followed by a 28-week open-label extension. At week 12 in phase 2b, HbA1c decreased by 1.10% with 1 mg and 1.43% with 3 mg (both p < 0.0001). At week 24 in phase 3, HbA1c decreased by 1.80% with Efsubaglutide 3 mg versus 0.74% with placebo (estimated treatment difference, -1.06%; p < 0.001). Adverse events were predominantly mild to moderate gastrointestinal events. Trial registration: ClinicalTrials.gov NCT04998032.
Authors
- Lin Cheng (ORCID: https://orcid.org/0000-0002-6031-3899)
- Hui Peng (ORCID: https://orcid.org/0000-0002-4573-1048)
- Pan Huanfeng
- X.C. Li (ORCID: https://orcid.org/0000-0002-5981-2762)
- Liping Li (ORCID: https://orcid.org/0000-0001-7396-1310)
- Shu Li (ORCID: https://orcid.org/0000-0003-0350-0353)
- Xi Zhang (ORCID: https://orcid.org/0000-0002-4638-3997)
- Wei Zhang (ORCID: https://orcid.org/0000-0001-7800-3189)
- Jin Zhou (ORCID: https://orcid.org/0000-0002-1534-2279)
- Junhua Song
- Yongcai Zhao
- Chengxia Jiang
- Qingju Li
- Chengyan Jiang
- Xiuhai Su
- Lili Zhang
- Xin Zheng
- Yulong Xu
- Jiao Sun
- Haifang Wang
- Yuqian Bao
- Tianshu Zeng
- Hongwei Ling
- Weiping Jia (ORCID: https://orcid.org/0000-0002-6244-2168)
- Jingyi Lu
- Fei Gao
- Ming Liu (ORCID: https://orcid.org/0000-0003-2665-4072)
- Li Mao
- Jianhua Ma
- Yihua Wang
- Xiaoxia Shi
- Yiming Li
- Yang Liu
- Qinghua Wang (ORCID: https://orcid.org/0000-0002-6478-0988)
- Xiaolin Dong
- Zhifeng Cheng
Institutions
- Qiqihar University (CN)
- Handan College (CN)
- Harbin Medical University (CN)
- Shanxi Medical University (CN)
- Xuzhou Medical College (CN)
- Yichun University (CN)
- Fudan University (CN)
- Tianjin Medical University General Hospital (CN)
- Daqing City People's Hospital (CN)
- People 's Hospital of Jilin Province (CN)
- Huaian First People’s Hospital (CN)
- Huadong Hospital (CN)
- Cangzhou Central Hospital (CN)
- Fosun Pharma (China) (CN)
- Jinan Central Hospital (CN)
- Affiliated Hospital of Xuzhou Medical College (CN)
- Affiliated Hospital of Taishan Medical University (CN)
- Fourth Hospital of Changsha (CN)
- Second Affiliated Hospital of Zhengzhou University (CN)
- People's Hospital of Cangzhou (CN)
- Nanyang Institute of Technology (CN)
- First People’s Hospital of Zunyi (CN)
- Fourth Affiliated Hospital of Harbin Medical University (CN)
- Wuhan Union Hospital (CN)
- Shanxi Jincheng Anthracite Mining Group (China) (CN)
- Second Hospital of Shanxi Medical University (CN)
- First Affiliated Hospital of Henan University of Science and Technology (CN)
- Nanyang Medical College (CN)
- Huizhou Central People's Hospital (CN)
- Heze Municipal Hospital (CN)
- The First People's Hospital of Guiyang (CN)
- Shanghai Sixth People's Hospital (CN)
- Second People’s Hospital of Yibin (CN)
- Huashan Hospital (CN)
- Shandong First Medical University (CN)
- Union Hospital (CN)
- Beijing Obstetrics and Gynecology Hospital (CN)
- Huazhong University of Science and Technology (CN)
- Nanjing Medical University (CN)
- Qiqihar Medical University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-05-08
- DOI
- https://doi.org/10.1038/s41467-026-72574-7
- Primary Topic
- Diabetes Treatment and Management
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Fudan University