1861-LB: Efficacy and Safety of HRS9531, a Novel Dual GLP-1/GIP Receptor Agonist, in Obese Adults—A Phase 2 Trial

Introduction: HRS9531, a novel dual GLP-1 and GIP receptor agonist, has shown prominent efficacy in glycemic control and weight loss in phase 1 trials. This phase 2 study evaluated the efficacy and safety of HRS9531 in obese adults without diabetes.

Methods: In this randomized, double-blind, placebo-controlled phase 2 study, 249 Chinese adults with a BMI of 28-40 kg/m² were randomized 1:1:1:1:1 to receive once-weekly subcutaneous injections of HRS9531 (1.0 mg, 3.0 mg, 4.5 mg, and 6.0 mg) or placebo for 24 weeks (24W). The primary endpoint was the percentage change in body weight at W24.

Results: The least-squares mean percentage change in body weight from baseline at W24 was -5.4% (95% CI -7.3% to -3.5%), -13.4% (-15.2% to -11.5%), -14.0% (-15.9% to -12.1%), and -16.8% (-18.8% to -14.9%) in the 1.0 mg, 3.0 mg, 4.5 mg, and 6.0 mg groups, respectively, compared to -0.1% (-2.1% to 1.8%) in the placebo group (P<0.0001 for all comparisons with placebo). The proportion of participants achieving ≥5% body weight reduction was 52.0%, 88.2%, 92.0%, 91.8%, and 10.2%, respectively. Additionally, HRS9531 outperformed placebo in lowering blood pressure, improving glycemic control, and reducing triglyceride levels. The least-squares mean changes from baseline to W24 in systolic blood pressure ranged from -4.46 to -8.33 mmHg in the HRS9531 groups (placebo: -0.41 mmHg) and in the waist circumference ranged from -5.14 to -12.73 cm in the HRS9531 groups (placebo: -1.82 cm). Most adverse events (AEs) were mild or moderate in severity, and the most common AEs were nausea, diarrhea, decreased appetite, and vomiting, occurring primarily during dose escalation. No serious AEs were treatment-related and no participants discontinued treatment due to treatment-related AEs.

Conclusion: HRS9531 effectively reduced body weight, blood pressure, blood glucose, and triglycerides, with a favorable safety profile. These data support further clinical development of HRS9531 for obesity treatment.