Obese Rhesus Monkeys Recapitulate Human Efficacy Profiles of Semaglutide, Bimagrumab, and Retatrutide

Introduction and Objective: Translational animal models that closely reflect human responses are critical for anti-obesity drug development. This study evaluated efficacy, body composition changes, and safety profiles of Semaglutide, Bimagrumab, and Retatrutide in obese rhesus monkeys. Methods: Twenty obese rhesus monkeys (BMI > 35, age 10-18 years) were randomized into four groups (n = 5/group): placebo, Semaglutide (30 mg/kg), Bimagrumab (3 mg/kg), and Retatrutide (0.06 mg/kg). Treatments were administered subcutaneously at clinically relevant dosing frequencies, followed by an 8-week observation period. Body weight, BMI, and body composition were assessed at baseline and post-treatment using DEXA and 3.0T MRI. Results: At baseline, mean body weight was 15.45 ± 2.38 kg, body fat content was 37.9 ± 9.2%, and lean mass was 8938 ± 1075 g. Imaging and quantitative assessments showed that increasing obesity severity was associated with higher body fat percentage and preferential accumulation of visceral fat. After 8 weeks, Semaglutide induced a significant 18% reduction in body weight and a 36% reduction in body fat content, accompanied by a 3% loss of lean mass (P < 0.05 vs. placebo). Bimagrumab resulted in a modest 3-4% reduction in body weight, a significant 26% reduction in body fat content, and an ~8% increase in lean mass (P < 0.01 vs. placebo), indicating selective fat loss with concomitant lean mass gain. Retatrutide produced a marked 20% reduction in body weight and a 45% decrease in body fat content, with minimal change in lean mass (~0.93%). Overall efficacy and tolerability profiles were consistent with clinical observations in humans. Conclusion: Obese rhesus monkeys exhibit human-like fat distribution and treatment responses to Semaglutide, Bimagrumab, and Retatrutide. Notably, the selective fat loss and lean mass gain induced by Bimagrumab closely mirror clinical findings, supporting this model as a robust translational platform for preclinical anti-obesity drug development. Disclosure: L. Gong: None. Z. Yang: None. Y. Liang: None. M. Wu: None. L. Yang: None. W. Zeng: None.