Abstract
Introduction and Objective: Efsubaglutide Alfa (Suba) is a novel long-acting GLP-1RA. This trial aimed to evaluate its efficacy and safety in overweight/obese participants (pts) with inadequate body weight (BW) control despite lifestyle interventions. Methods: This double-blind, placebo (PBO)-controlled trial (NCT06732960) randomized pts into Suba or PBO groups in 8:2 across five dose groups (5, 7.5, 10, 15, and 20 mg). Pts underwent biweekly dose escalation to achieve target doses, and maintained for 4 weeks for efficacy and safety evaluation. The primary endpoints were the BW change (%) from baseline and the proportion of pts achieving ≥5% weight loss after 4 weeks at target doses. Results: 50 pts were enrolled (mean age: 36.3 years; mean BMI: 33.0 kg/m²). The mean BW reduction by Suba was -7.2% (-6.5 kg) vs. PBO -0.9% (-0.5 kg). 84.6% of pts in Suba groups achieved ≥5% weight loss (PBO: 0%). Mean fat mass decreased by 4.5 kg (13.1%) (PBO: -0.2 kg, -1.2%), and the ratio of muscle-to-fat mass increased significantly by 19.7% (PBO: 0.6%). Treatment-related adverse events were mostly mild to moderate gastrointestinal, with no premature discontinuations, SAEs, or hyperglycemia. Conclusion: Suba showed a favorable safety profile and significant weight loss in overweight/obese pts. Most pts achieved clinically meaningful weight loss target, indicating Suba's potential as an effective weight management option.