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The C18 fatty diacid-albumin binding mechanism that extends Semaglutides half-life to one week also modifies its receptor pharmacology in important ways relative to native GLP-1 , the albumin-bound form of Semaglutide that constitutes the pharmacokinetically relevant circulating species interacts with GLP-1R through a receptor engagement profile influenced by the bulky albumin-fatty acid complex, potentially modifying receptor internalisation kinetics, biased signalling between Gs, Gq/11, and beta-arrestin pathways, and the duration and amplitude of downstream signalling relative to native GLP-1 or shorter-acting analogues
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Ipamorelin does not produce these additional effects, making it preferred in studies requiring a pure GH signal
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