Tirzepatide is a dual agonist of the GIP and
GLP-1 receptors. Tirzepatide is an analogue of gastric inhibitory polypeptide
(GIP), a human hormone that stimulates insulin release from the pancreas.
Tirzepatide is a linear polypeptide of 39 amino acids, chemically modified by
lipidation to improve its cellular uptake and metabolic stability.
Indication
Treatment of type 2 diabetes mellitus and
weight loss. Tirzepatide is used to improve glycemic control in combination
with diet and exercise.
Mechanism of
Action
Tirzepatide has a higher affinity for GIP receptors than for GLP-1
receptors, and this dual agonist action provides a more pronounced reduction in
hyperglycemia compared to a selective GLP-1 receptor agonist. Tirzepatide
mimics the action of natural GIP on the GIP receptor. At the GLP-1 receptor,
tirzepatide preferentially forms cAMP (a messenger involved in the regulation
of glycogen, sugar, and lipid metabolism) rather than attracting beta-arrestin.
This combination of its preference for the GIP receptor and the specific
signaling properties of GLP-1 increases insulin secretion. Tirzepatide
increases levels of both adiponectin and adipokine, which are involved in the
regulation of both glucose and lipid metabolism, with a maximum increase of 26%
from baseline after 26 weeks at a dose of 10 mg.
