Tirzepatide Mechanism of Action

Tirzepatide displays imbalanced dual receptor agonism, with higher affinity and potency at the GIP receptor than the GLP-1 receptor . At the GLP-1R, tirzepatide demonstrates biased agonism toward cAMP generation while minimizing β-arrestin recruitment, which may preserve receptor surface expression and enhance cellular response . The peptide also activates GIPR with balanced signaling properties. Together, these mechanisms enhance glucose-stimulated insulin secretion, suppress glucagon release, and modulate adipocyte nutrient metabolism through complementary incretin pathways.