Introduction and Objective: This study aimed to evaluate efficacy, safety, and tolerability of novel once-daily oral small-molecule GLP-1 receptor agonist DA-302168S in Chinese non-diabetic adults with overweight or obesity. Methods: This double-blind phase 2 trial enrolled 250 Chinese adults with obesity (Body Mass Index (BMI) ≥28 kg/m²) or overweight (BMI ≥24 kg/m² plus ≥1 obesity-related comorbidity). Participants were assigned (1:1:1:1) to 5, 10, 20 or 30 mg dose cohorts, then randomized (3:1) to DA-302168S or placebo per cohort. Primary endpoint was percentage change in body weight (BW) from baseline to week 16. Results: Baseline mean BW 86.59 kg, BMI 31.63 kg/m². At week 16, DA-302168S showed distinct dose-response weight loss effect, with maximal mean reductions of 10.22% (FAS) and 10.72% (PPS). All DA-302168S doses yielded significantly greater improvements versus placebo in BW reduction, ≥5% weight loss rates, waist circumference and blood pressure (BP). The most frequent adverse events (AEs) were mild gastrointestinal (GI) reactions (nausea, vomiting), mainly during titration. Treatment was well-tolerated, with a GI-related discontinuation rate of 0.8%. No serious AEs were reported. Conclusion: DA-302168S induced robust clinically meaningful weight loss with improved cardiometabolic risk factors (BP, waist circumference) and favorable safety profile, supporting its further development as oral weight management therapy. Disclosure L. Ji: None. Y. Luo: None. G. Dong: None. Z. Yu: None. Funding Chengdu DIAO Pharmaceutical Group Co., Ltd.
JI et al. (Fri,) studied this question.