This podcast explores the evolving landscape of treatments for obesity and diabetes, highlighting glucagon-like peptide-1 (GLP-1) receptor agonists and their progression to multi-agonist medications targeting additional receptors for enhanced efficacy. The initial source details the mechanisms, currently available options, and limitations of these therapies, including barriers to access and emerging drug discovery directions like triple agonists such as UBT251 acquired by Novo Nordisk to compete with existing treatments. The updated synthesis expands on this by examining the potential of natural compounds and rationally designed small-molecule polypharmacology as alternative and complementary approaches, addressing the challenges and future possibilities of integrating these strategies for improved metabolic disease management. Produced by Dr. Jake Chen