Introduction and Objective: RAY1225, a bi-weekly GLP-1/GIP receptor agonist, has demonstrated substantial potential for glycemic control and weight loss in phase 1 study. This phase 2 trial assessed the efficacy and safety of RAY1225 compared with placebo in Chinese overweight or obese adults without diabetes. Methods: In this multicenter, randomized, double-blind, placebo-controlled phase 2 trial, nondiabetic Chinese adults with BMI ≥28 kg/m² (or 24-28 kg/m² plus comorbidity) were enrolled. Participants (N=231; mean weight 92.34 kg, BMI 32.72 kg/m², age 34.0 years, 60.1% male) were randomized to RAY1225 (3, 6, 9, 12, 15, or 18 mg) or placebo. The primary endpoint was percent body weight change from baseline to week 24. Results: Weight reduction at week 24 was dose-dependent. LS mean % changes for RAY1225 were -9.73% (3mg), -12.68% (6mg), -14.75% (9mg), -14.13% (12mg), -14.92% (15mg), and -21.18% (18mg), versus -2.96% for placebo (all p0.001). Significantly more participants achieved ≥5%, ≥10%, and ≥15% weight loss with RAY1225. Treatment also improved waist circumference, BMI, SBP, DBP, triglycerides, and uric acid vs. placebo. The most common AEs were gastrointestinal (nausea, vomiting), with low incidence and mild-to-moderate severity. No drug-related serious AEs occurred. Conclusion: Bi-weekly RAY1225 demonstrates significant weight loss and metabolic benefits in overweight/obese nondiabetic individuals, with a favorable safety profile. Disclosure L. Ji: None. L. Yan: None. M. Xu: None. L. Gao: Consultant; Current; Innovent Biologics, Inc. X. Xia: None. C. Wang: None. Y. Zhu: None. J. Li: Employee; Current; Guangdong Raynovent Co., Ltd. Y. Peng: Employee; Current; Guangdong Raynovent Co., Ltd. H. Li: Employee; Current; Guangdong Raynovent Co., Ltd. X. Chen: Employee; Current; Guangdong Raynovent Biotech Co., Ltd.
JI et al. (Sun,) studied this question.