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The critical design decisions included: GIP backbone selection : Starting from GIP rather than GLP-1, as GIP naturally has weak cross-reactivity with GLP-1R, providing a scaffold for optimization Aib2 substitution : Replacing Ala2 with alpha-aminoisobutyric acid for DPP-4 resistance (identical strategy to semaglutide) C-terminal extension : Adding a GGPSSGAPPPS (Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser) 11-residue C-terminal extension that enhances GLP-1R binding C-20 fatty diacid acylation : Attaching an eicosanedioic acid (C-20 diacid) at Lys20 via a Glu-2xOEG linker for albumin binding The resulting molecule exhibits approximately 5:1 selectivity for GIPR over GLP-1R it is a full GIPR agonist and a partial GLP-1R agonist, yet clinically achieves superior outcomes to selective full GLP-1R agonists [7]

Many cyanocobalamin injection products are stored at room temperature and protected from light, but the label on your dispensed product should guide handling

Acknowledgements This work was supported by the Tehran University of Medical Sciences, Deputy of Research

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