Mounjaro Receptor Mechanism of Action
Mounjaro (tirzepatide) is a dual agonist that acts on both GLP-1 (glucagon-like peptide-1) receptors and GIP (glucose-dependent insulinotropic polypeptide) receptors. 1
Dual Receptor Activation
Tirzepatide is engineered as an acylated peptide that simultaneously activates both the GIP receptor and the GLP-1 receptor, representing a novel mechanism distinct from single-receptor GLP-1 agonists like semaglutide 2
These receptors are key mediators of insulin secretion and are also expressed in regions of the brain that regulate food intake, explaining tirzepatide's effects on both glucose control and appetite suppression 2
The dual-hormone agonist mechanism provides enhanced metabolic benefits including delayed gastric emptying, suppressed appetite, improved insulin secretion, reduced glucagon secretion, and increased pancreatic β-cell growth 1
Receptor Binding Characteristics
Tirzepatide's affinity for the GLP-1 receptor is approximately five times less than that of endogenous GLP-1, yet it still produces potent clinical effects 1
The molecule demonstrates biased GLP-1 receptor activation and may cause GIP receptor downregulation, suggesting a more complex mechanism than simple dual agonism 3
Clinical Implications of Dual Receptor Action
The dual GIP/GLP-1 activation produces synergistic effects on insulin response and glucagon suppression through the natural incretin system, where both hormones are released from intestinal cells in response to nutrient intake 1
This dual mechanism results in superior weight loss (20.9% at 72 weeks) compared to selective GLP-1 receptor agonists like semaglutide (14.9%), along with greater HbA1c reduction 1, 4
The anorexigenic effects are potentiated by dual GIP-GLP-1 activation, working through multiple pathways including central appetite suppression, delayed gastric emptying, and increased energy expenditure 1