Efficacy and Safety of Chemically Synthesized Semaglutide Injection ( HD1916 ) for the Treatment of Obesity: A Multicenter, Randomized, Phase III Trial

Abstract

ABSTRACT Aims To evaluate whether HD1916, a chemically synthesised semaglutide, is therapeutically equivalent to the reference product semaglutide (Wegovy) in body weight reduction among Chinese adults with obesity without diabetes. Materials and Methods This multicenter, randomised, open‐label, active‐controlled Phase III trial was conducted at 30 centers in China. Adults aged 18–75 years with obesity (BMI ≥ 28 kg/m 2 ) and without diabetes were randomised 1:1 to receive once‐weekly subcutaneous HD1916 or semaglutide for 44 weeks. The primary endpoint was the percentage change in body weight from baseline to week 44. Equivalence was established if the 95% confidence interval (CI) of the between‐group difference was within the prespecified margin of ±4.16%. Key secondary endpoints included the proportions of participants achieving ≥ 5% and ≥ 10% weight loss and change in waist circumference. Results A total of 462 participants were randomised (231 per group). At week 44, mean body weight decreased by 13.1% with HD1916 and 14.4% with semaglutide. The estimated treatment difference was 1.35% (95% CI, −0.02 to 2.72), which fell within the equivalence margin, confirming therapeutic equivalence. Proportions of participants achieving ≥ 5% weight loss (87.8% vs. 90.5%) and ≥ 10% weight loss (68.7% vs. 73.6%), as well as reductions in waist circumference, were comparable between groups. Any‐grade treatment‐emergent adverse events occurred in 86.5% and 89.2% of participants in the HD1916 and semaglutide groups, respectively; most were Grade 1–2. Conclusions HD1916 demonstrated equivalent body weight reductions to the reference product semaglutide (Wegovy), with a comparable safety profile.