GIP (glucose-dependent insulinotropic polypeptide) is a potent incretin hormone secreted from enteroendocrine K cells within minutes of nutrient ingestion 1. Its primary function is glucose-dependent stimulation of insulin secretion from pancreatic β-cells, playing a greater physiological role as an incretin compared to GLP-1 2. GIP signals through G-protein-coupled receptors on β-cells, activating adenylate cyclase and cAMP/PKA pathways to promote insulin secretion, with β-arrestin 2 playing distinct modulatory roles in this signaling 3. Beyond glucose homeostasis, GIP exhibits pleiotropic functions including promotion of energy storage via direct adipose tissue actions and enhancement of bone formation through osteoblast stimulation 1. However, in type 2 diabetes, GIP loses much of its acute insulinotropic activity despite relatively normal secretion 2. Clinically, GIP represents an important therapeutic target. Dual GLP-1/GIP receptor agonists like tirzepatide demonstrate superior efficacy for glycemic control and weight reduction compared to selective GLP-1 agonists 2, while GIPR antagonism combined with GLP-1R agonists produces additive weight loss 4. GIP agonist effects on metabolic disease appear mediated indirectly through improvements in insulin resistance and glycemic control rather than direct hepatic actions 5.