Dual incretin agonism describes the pharmacological strategy of activating both the glucose-dependent insulinotropic polypeptide (GIP) receptor and the glucagon-like peptide-1 (GLP-1) receptor with a single molecule. Tirzepatide is the first clinically approved dual incretin receptor agonist.
The rationale is complementary rather than additive coverage: GIP and GLP-1 receptors are expressed on overlapping but non-identical cell populations — β-cells, α-cells, adipocytes, vagal afferents and central satiety circuits — and combined engagement broadens the incretin response beyond what a mono-agonist such as Semaglutide can achieve.
Dual incretin agonism is the defining pharmacological concept behind Tirzepatide and a stepping stone to triple agonists such as Retatrutide.