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)

  • Nat Commun. 2026 May 8;17(1):6222. doi: 10.1038/s41467-026-72574-7.
Weiping Jia  #  1 ,  Fei Gao  #  2 ,  Jingyi Lu  #  2 ,  Zhifeng Cheng  3 ,  Xiaolin Dong  4 ,  Xiaoxia Shi  5 ,  Xiuhai Su  6 ,  Liping Li  7 ,  Wei Zhang  8 ,  Yihua Wang  9 ,  Jianhua Ma  10 ,  Shu Li  11 ,  Haifang Wang  12 ,  Lin Cheng  13 ,  Li Mao  14 ,  Chengyan Jiang  15 ,  Qingju Li  16 ,  Xing Li  17 ,  Xin Zheng  18 ,  Ming Liu  19 ,  Jiao Sun  20 ,  Hui Peng  21 ,  Huanfeng Pan  22 ,  Hongwei Ling  23 ,  Chengxia Jiang  24 ,  Junhua Song  25 ,  Xinhuan Zhang  26 ,  Lili Zhang  27 ,  Yang Liu  28 ,  Tianshu Zeng  29 ,  Yongcai Zhao  30 ,  Yulong Xu  31 ,  Yiming Li  32 ,  Yuqian Bao  2 ,  Jian Zhou  2 ,  Qinghua Wang  33  34
Affiliations
  • 1. Department of Endocrinology and Metabolism, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital, Shanghai Clinical Centre for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China. [email protected].
  • 2. Department of Endocrinology and Metabolism, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital, Shanghai Clinical Centre for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China.
  • 3. Department of Endocrinology and Metabolism, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
  • 4. Department of Endocrinology and Metabolism, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, China.
  • 5. Department of Endocrinology and Metabolism, The First Affiliated Hospital of Nanyang Medical College, Nanyang, China.
  • 6. Department of Endocrinology and Metabolism, Cangzhou Hospital of Integrated TCM-WM Hebei, Cangzhou, China.
  • 7. Department of Endocrinology and Metabolism, The First Affiliated Hospital of Henan University of Science & Technology, Luoyang, China.
  • 8. Department of Endocrinology and Metabolism, The First Hospital of Qiqihar, Qiqihar, China.
  • 9. Department of Endocrinology and Metabolism, Nanyang First People's Hospital, Nanyang, China.
  • 10. Department of Endocrinology and Metabolism, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
  • 11. Department of Endocrinology and Metabolism, Huizhou Central People's Hospital, Huizhou, China.
  • 12. Department of Endocrinology and Metabolism, Handan First Hospital, Handan, China.
  • 13. Department of Endocrinology and Metabolism, Heze Municipal Hospital, Heze, China.
  • 14. Department of Endocrinology and Metabolism, Huai'an First People's Hospital, Huai'an, China.
  • 15. Department of Endocrinology and Metabolism, First People's Hospital of Zunyi, Zunyi, China.
  • 16. Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • 17. Department of Endocrinology and Metabolism, Second Hospital of Shanxi Medical University, Taiyuan, China.
  • 18. Department of Endocrinology and Metabolism, Beijing Boai Hospital, Beijing, China.
  • 19. Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.
  • 20. Department of Endocrinology and Metabolism, Huadong Hospital, Shanghai, China.
  • 21. Department of Endocrinology and Metabolism, Yichun People's Hospital, Yichun, China.
  • 22. Department of Endocrinology and Metabolism, Jilin People's Hospital, Jilin, China.
  • 23. Department of Endocrinology and Metabolism, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
  • 24. Department of Endocrinology and Metabolism, The Second People's Hospital of Yibin, Yibin, China.
  • 25. Department of Endocrinology and Metabolism, The Fourth Hospital of Changsha, Changsha, China.
  • 26. Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Shandong First Medical University, Taian, China.
  • 27. Department of Endocrinology and Metabolism, Jincheng General Hospital, Jincheng, China.
  • 28. Department of Endocrinology and Metabolism, Daqing People's Hospital, Daqing, China.
  • 29. Department of Endocrinology and Metabolism, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 30. Department of Endocrinology and Metabolism, Cangzhou Central Hospital, Cangzhou, China.
  • 31. Shanghai Innogen Pharmaceutical Technology Co., Ltd., Shanghai, China.
  • 32. Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical School, Fudan University, Shanghai, China.
  • 33. Shanghai Innogen Pharmaceutical Technology Co., Ltd., Shanghai, China. [email protected].
  • 34. Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical School, Fudan University, Shanghai, China. [email protected].
  • # Contributed equally.
PMID: 42103705 DOI: 10.1038/s41467-026-72574-7
Abstract

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.

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