1034-OR: Efficacy and Safety of Dual GLP-1/GIP Receptor Agonist HDM1005 in Obese Participants without Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial

Introduction and Objective: HDM1005 is a long-acting GLP-1R/GIPR peptide dual agonist that exhibit promising efficacy in weight loss in phase 1 trials. This phase 2 study evaluated its efficacy and safety in Chinese obese adults. Methods: In this multi-center, randomized, double-blind, placebo-controlled trial (NCT06886126), 243 non-diabetic adults with BMI of 28-40 kg/m2 were randomized 1:1:1:1:1 to once-weekly subcutaneous HDM1005 0.5 mg, 1.0 mg, 2.0 mg, and 4.0 mg or placebo for 22 weeks (22W), with dose escalated every 4W. The primary endpoint was the percentage change in body weight from baseline to W22. Secondary endpoints included changes in cardiometabolic parameters. Safety was monitored throughout. Results: Using a treatment-policy estimand, the study results showed that the body weight reduction from baseline for HDM1005 groups of 0.5 mg, 1.0 mg, 2.0 mg, and 4.0 mg were 7.38%, 9.61%, 13.21%, and 13.32%, respectively vs placebo 2.45% (all p<0.0001). Correspondingly, 24.0%, 52.1%, 75.0%, and 70.8% of participants in HDM1005 groups achieved ≥10% weight loss vs 6.1 % with placebo. HDM1005 also improved cardiometabolic parameters from baseline (difference relevant to placebo) in waist circumference (up to -7.27 cm), SBP (up to -10.19 mmHg), DBP (up to -6.13 mmHg), TG (up to -36.99%), LDL-C (up to -8.19%) and non-HDL-C (up to -11.88%). Additionally, HDM1005 also showed great improvements in FPG and HbA1c. AEs were mostly mild or moderate gastrointestinal symptoms (decreased appetite, diarrhoea, nausea, vomiting). Nausea incidence ranged from 2.1% to 18.8% across HDM1005 doses vs 2.0% with placebo; vomiting ranged from 0% to 12.5% vs 4.1%. No participant permanently discontinued treatment due to AE and no SAE was treatment-related. Conclusion: HDM1005 showed clinically meaningful dose-dependent weight loss, and improved blood pressure, blood glucose and lipid profiles, with excellent safety and tolerability in Chinese adults with obesity. Disclosure X. Li: None. L. Zhao: None. Y. Lu: None. J. Yao: None. Z. Cheng: None. H. Lang: None. L. Fu: None. J. Song: None. F. He: Employee; Current; HuaDong Pharmaceutical Co.Ltd. H. Lu: Employee; Current; Huadong Medicine Co., Ltd. L. Shen: None. L. Zhong: Employee; Current; HuaDong Pharmaceutical Co., Ltd. J. Xu: Employee; Current; Huadong Medicine Co., Ltd. Stock/Shareholder; Current; Huadong Medicine Co., Ltd.