Introduction and Objective: Lean mass loss during pharmacologic weight reduction remains a key limitation of current obesity therapies. BG-104 is a multi-pathway therapeutic integrating GLP-1, GIP, and human growth hormone (hGH) receptor agonism with Activin Type II Receptor (ActRII) targeting to promote adiposity reduction while preserving skeletal muscle. Methods: Metabolic and body composition effects were evaluated in aged diet-induced obese mice maintained on a high-fat diet for 22-weeks and treated with BG-104 every four days (Q4D), with vehicle and tirzepatide (Q2D and Q4D). Results: BG-104 produced body weight reduction comparable to tirzepatide, while body composition analysis demonstrated robust fat mass reduction with superior preservation of lean mass. Notably, ~99.5% of total weight loss was attributable to fat mass, indicating highly selective adiposity reduction with minimal lean mass decline. Conclusion: These findings suggest that multi-pathway targeting of incretin and anabolic signaling may improve the quality of weight loss and represents a differentiated metabolic therapeutic approach with potential relevance for obesity and sarcopenic obesity. Disclosure Y. Jeon: None. Y. Seo: None. R. Sung: None. Y. Sung: None.
JEON et al. (2026) studied this question.