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This group includes semaglutide (Ozempic and Wegovy), tirzepatide (Mounjaro and Zepbound), liraglutide, and dulaglutide

In vivo studies using Wistar rats in which honey was ingested with Aloe vera showed that these apoptotic effects complement the cell cycle arrest described in Section 4.1 (59)

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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]

Targeting hepatic stellate cells for the prevention and treatment of liver cirrhosis and hepatocellular carcinoma: strategies and clinical translation