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The three receptors targeted by retatrutide are: GLP-1R (Glucagon-like peptide-1 receptor) a well-established target already exploited by approved medicines such as semaglutide and liraglutide GIPR (Glucose-dependent insulinotropic polypeptide receptor) also targeted by tirzepatide in combination with GLP-1R GCGR (Glucagon receptor) an additional target that distinguishes retatrutide from currently approved dual agonists This triple mechanism of action places retatrutide in a distinct pharmacological class

Activation of Notch signaling and the expression of its downstream target gene, hairy and enhancer of split 1 ( Hes1 ) in TA cells repress the expression of transcription factors crucial for entry into the secretory lineage including atonal homolog 1 ( Atoh1 ) and induce absorptive cell fate commitment