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The Aib 13 of tirzepatide seems to lower its GLP-1 activity without affecting its GIP activity, and to destroy its GCG activity

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In contrast, the exendin-P5 mutagenesis profile was very distinct from the other peptides with few mutations altering exendin-P5 affinity and only a very weak, albeit significant, correlation with the effect of mutations on GLP-1 in cAMP signalling assays (Figures 4-5, Supplemental Figures 9-10)