Synthetic Semaglutide Injection Achieves Non-Inferior Weight Loss to Wegovy in Obese Adults

The global prevalence of obesity continues to rise, posing significant public health challenges due to its association with numerous comorbidities like type 2 diabetes mellitus, hypertension, and dyslipidemia. While lifestyle interventions are foundational, pharmacological treatments are often necessary for sustained weight loss. Glucagon-like peptide-1 receptor (GLP-1R) agonists, such as semaglutide, have emerged as highly effective options by regulating appetite and glucose metabolism. However, accessibility and cost can limit their widespread use, creating a need for equally efficacious and safe alternative formulations to expand treatment options.

This randomized, Phase III, non-inferiority study enrolled 270 adults with obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) with at least one weight-related comorbidity (hypertension, dyslipidemia, or type 2 diabetes). Patients were randomized (2:1) to receive either Test semaglutide (N=177) or Reference semaglutide (N=90) once weekly via injection. The dose was escalated from 0.25 mg to 2.4 mg over the study period. The primary endpoint was the percentage change in bodyweight from baseline to Week 24, with secondary endpoints including changes in BMI, waist circumference, quality of life (SF-36), and glycemic parameters.

Out of 267 randomized patients, 246 completed the study. At Week 24, the mean percent weight change from baseline was -13.8% ± 4.28% in the Test semaglutide group and -14.1% ± 4.11% in the Reference semaglutide group. The least-squares mean difference was 0.26% (95% CI: -0.86% to 1.39%), which successfully met the criterion for non-inferiority. This indicates that the synthetic semaglutide was statistically comparable to the reference product in terms of weight loss efficacy.

The proportion of patients achieving ≥5% weight loss was 96.40% in the Test group and 98.80% in the Reference group, while ≥10% weight loss was achieved by 80.60% and 80.00% of patients, respectively.

Improvements in body mass index, waist circumference, SF-36 total score, and glycemic parameters were also comparable between both groups. Treatment-emergent adverse events were reported in 72.30% of the Test group and 76.70% of the Reference group, with gastrointestinal events being the most common, consistent with known side effects of GLP-1R agonists.