Core Viewpoint - The article highlights the positive results of the Phase II clinical trial for HDM1005, a GLP-1R/GIPR dual agonist developed by Huadong Medicine, demonstrating significant weight loss efficacy and good safety profile [4][9]. Mechanism of Action - HDM1005 activates both GLP-1R and GIPR, promoting cAMP production, which enhances insulin secretion, suppresses appetite, delays gastric emptying, and improves overall metabolic function [5]. - The drug also shows potential benefits in reducing plasma volume, lowering oxidative stress and systemic inflammation, and improving cardiovascular adaptability, indicating multiple therapeutic values including weight loss and glycemic control [5]. Phase II Study Design - The Phase II clinical trial included 243 participants over a 22-week treatment period, with a balanced comparison of baseline metrics such as weight, waist circumference, and BMI across dosage groups [6]. - The study employed a dose-escalation strategy with four dosage groups (0.5 mg, 1.0 mg, 2.0 mg, and 4.0 mg) compared to a placebo group [6]. Significant Weight Loss Results - The results indicated that participants in the highest dosage group (4.0 mg) experienced a weight reduction of 13.28% from baseline, while the placebo group saw a decrease of only 2.46% [7]. - The proportion of participants achieving a weight loss of ≥10% was notable: 75.0% in the 2.0 mg group and 70.8% in the 4.0 mg group, compared to 6.1% in the placebo group [7]. - Improvements in waist circumference (6.3–10.3 cm reduction) and BMI (2.4–4.2 kg/m² reduction) were also observed, alongside significant enhancements in various metabolic indicators [7]. Safety Profile - HDM1005 demonstrated a good safety and tolerability profile, with adverse events primarily being mild to moderate, and no serious treatment-related adverse events reported [8]. - Common side effects included decreased appetite and gastrointestinal reactions, with nausea and vomiting rates varying across dosage groups [8]. Overall Summary - HDM1005 shows strong weight loss effects, a clear dose-response relationship, and a favorable safety profile, positioning it for differentiated development within the competitive landscape of GLP-1 drugs [9].