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Mechanistically, retatrutide adds a third receptor (glucagon) that tirzepatide doesnt engage at all, and binds the GIP receptor far more tightly, so meaningful GIP engagement arrives at a fraction of the dose
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Pharmacol Rev (2010) 62(4):72659
[1] It is also known as tetra-substituted GRF (1-29), and is composed of a sequence thought to be the smallest necessary to interact with GHRH receptors, specifically the first 29 amino acids of GHRH