2849-LB: Efficacy and Safety of cAMP-Biased Ecnoglutide vs. Unbiased Semaglutide in Adults with Obesity: Twenty-Week Results from a Multicenter, Randomized, Open-Label, Phase 2 Study

Introduction and Objective: cAMP-biased GLP-1 analogues represent a promising approach to enhance efficacy compared to unbiased analogues like semaglutide; however, direct head-to-head clinical evidence remains limited. Ecnoglutide is a novel cAMP-biased GLP-1 analogue approved for the treatment of type 2 diabetes mellitus and overweight/obesity. The trial aimed to compare the efficacy and safety of ecnoglutide versus semaglutide in adults with obesity. Methods: This ongoing Phase 2, multicenter, randomized, open-label trial enrolled 163 adults with obesity (body mass index BMI ≥ 30 kg/m²) across 17 sites in China. Participants were randomized (1:1) to receive once-weekly subcutaneous injections of either ecnoglutide or semaglutide for 60 weeks. A pre-planned interim analysis was conducted at week 20, following dose escalation to a maintenance dose of 2.4 mg sustained for 4 weeks in both groups, to assess efficacy and safety in all enrolled patients (ClinicalTrials.gov ID: NCT07073417). Results: At week 20, the least-squares mean percentage change in body weight was -12.8% (95% CI, -13.7 to -11.8) in the ecnoglutide group and -9.5% (95% CI, -10.4 to -8.5) in the semaglutide group (P 0.0001). Participants in the ecnoglutide group were more likely than those in the semaglutide group to achieve weight reductions of at least 5%, 10%, and 15%. Both treatments were well tolerated. The most common adverse events were gastrointestinal disorders of mild to moderate severity: diarrhea (30.5% vs 30.9%), nausea (13.4% vs 21.0%), constipation (17.1% vs 11.1%), and vomiting (11.0% vs 12.3%) for ecnoglutide and semaglutide, respectively. Conclusion: This 20-week interim analysis demonstrated that ecnoglutide provides greater body weight reduction compared to semaglutide at the same dose level, with a comparable safety and tolerability profile. The ongoing trial will further evaluate the long-term efficacy and safety of ecnoglutide. Disclosure L. Ji: None. L. Gao: Consultant; Current; Innovent Biologics, Inc. H. Xue: None. L. Fu: None. K. Wang: None. X. Zhang: None. Q. Li: None. Y. Zhang: None. B. Wen: None. Y. Liu: None. S. Li: None. G. Sheng: None. C. Guiling: None. J. Han: None. H. Lang: None. X. Shi: None. Z. Zhang: None. L. He: None. H. Ding: None. Q. Zheng: Employee; Current; Hangzhou Sciwind Biosciences Co., Ltd. Stock/Shareholder; Current; Hangzhou Sciwind Biosciences Co., Ltd. M. Yang: Employee; Current; Sciwind bioscience, Sciwind bioscience. J. Ning: Employee; Current; Hangzhou Sciwind Biosciences Co., Ltd. Stock/Shareholder; Current; Hangzhou Sciwind Biosciences Co., Ltd. M. Guo: None. Y. Li: None. H. Pan: Stock/Shareholder; Current; Hangzhou Sciwind Biosciences Co., Ltd.