2580-P: Multimodal Imaging Reveals Organ- and Depot-Specific Adipose Tissue and Lean Mass Changes upon Weight-Loss Pharmacotherapy in NHPs

Introduction and Objective: Accurate, non-invasive body composition assessment is vital for evaluating anti-obesity therapies, yet conventional methods often lack resolution to distinguish beneficial fat loss from unintended lean mass reduction. To validate a high-resolution, multimodal imaging platform, we used semaglutide, a GLP-1 agonist with known effects on fat and muscle, as a positive control in male cynomolgus monkeys. Methods: Twelve animals were randomized to vehicle (n=6) or subcutaneous semaglutide (30 µg/kg, twice weekly; n=6) for 8 weeks. Primary outcomes included percent changes in total fat/lean mass (DEXA) and regional compartments (MRI): abdominal subcutaneous/visceral fat (SAT and VAT), liver PDFF, thigh/gluteal muscle volume, myocardial/skeletal muscle PDFF, and epicardial adipose tissue (EAT). Between-group differences were assessed via t-tests Results: The platform precisely captured semaglutide-induced body composition changes. At week 8, semaglutide reduced total fat mass by 28.60% vs. 3.22% rise in controls (p<0.001), with SAT (−38.75% vs. +4.40%; p<0.001) and VAT (−41.11% vs. +4.72%; p<0.001) reductions. Liver PDFF decreased by 24.48% with semaglutide vs. 13.85% rise in controls (p=0.014). Notably, significant lean mass loss (−10.05% vs. +1.50%; p<0.001) and thigh/gluteal muscle volume reduction (−10.10% vs. +1.79%; p<0.001) were detected. Additional metrics (skeletal muscle PDFF, LV-PDFF, EAT volume) were robustly quantified, showing comprehensive tissue-level resolution. Conclusion: In this non-human primate study, semaglutide elicited characteristic adipose/ectopic fat reductions and lean mass loss, all precisely captured by the multimodal DEXA-MRI platform. These results validate its sensitivity, reproducibility and discriminatory power in detecting known pharmacological effects on body composition, supporting its utility as translational tool for preclinical evaluation of obesity therapeutics. Disclosure K. Tian: None. Z. Zhu: None. L. Yang: None. R. Perez: None.