853-P: Efficacy and Safety of a Novel Dual GLP-1/GIP Receptor Agonist (HRS9531), in Obese Adults without Diabetes—Up to 52-Week Treatment

作者：Lin Zhao, Dan Zhu, Tianrong Pan, D WANG, Hongwei Ling, Ya Li, Cai H, Zhifeng Cheng, Dexue Liu, YUAN HUI, XIANFENG ZHANG, Hong Chen, YUE ZUO, YUQI SUN, Xiaoying Li · 发表于：Diabetes · 年份：2025 · DOI：10.2337/db25-853-p · 被引用次数：2 · 研究领域：Diabetes Treatment and Management、Metabolism, Diabetes, and Cancer、Pharmacology and Obesity Treatment

Introduction and Objective: HRS9531, a dual GLP-1/GIP receptor agonist (RA), has shown promising weight loss efficacy over 24 weeks (wks). This study evaluated its long-term efficacy and safety in obese adults without diabetes up to 52 wks. Methods: Chinese adults with a BMI of 28-40 kg/m² were randomized (1:1:1:1:1) to receive once-weekly (QW) subcutaneous injections of HRS9531 (1.0, 3.0, 4.5, or 6.0 mg) or placebo (PBO) for 24 wks (core treatment), followed by a 28-wk extension. During the extension, doses were maintained for 8 wks, after which all participants (pts) received HRS9531 for 20 wks: the PBO and 1.0 mg groups switched to 3.0 mg QW, while the others were re-randomized to QW or biweekly (Q2W) dosing. Results: Of 249 enrolled pts, 240 (96.8%) completed the 24-wk core treatment; 168 pts entered the extension, and 166 (98.8%) completed the 32-wk PBO-controlled treatment. At wk 32, pts treated with HRS9531 achieved up to a 17.97% reduction in mean body weight (BW) compared to 0.74% in the PBO group, with proportions achieving ≥5% and ≥10% BW reductions as high as 100.0% and 77.6%, respectively, vs. 12.5% and 6.1% in the PBO group. The mean percentage change in BW from wk 32 to wk 52 ranged from -0.76% to 0.01% in the HRS9531 Q2W groups, and from -3.45% to -0.02% in the HRS9531 QW groups. The Q2W dosing effectively maintained weight stability without rebound. TEAEs were reported in 75.5-91.8% of pts across the HRS9531 groups, compared to 85.7% in the PBO group during t...