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The linear peptide is covalently bound to a C20 fatty diacid moiety at the side chain of the Lys20 amino acid ( Figure 2 depicts the amino acid sequence of tirzepatide in comparison to GLP-1, GIP as well as the GLP-1RA exendin-4 (exenatide)
Furthermore, studies using a peripherally administered exenatide analogue conjugated to vitamin B12, which is sterically hindered from accessing regions protected by the blood brain barrier, improves glucose control in comparable fashion to unmodified exenatide, presumably at the level of the -cell, but does not induce emesis in the house musk shrew ( Suncus murinus) or rats (78, 79)
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