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Sharing a 94% structural homology with native human GLP-1, Semaglutide is distinguished by three modifications: 1) amino-acid substitutions at position 8 (alanine to -aminoisobutyric acid or Aib) and position 34 (lysine to arginine), and acylation of the lysine in position 26 with a spacer consisting of two 8-amino-3,6-dioxaoctanoic acid (ADO) moieties, a glutamic acid moiety, and a C-18 fatty di-acid side chain (Lau et al., 2015)
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Quick Comparison Feature CagriSema Retatrutide Development owner Novo Nordisk Eli Lilly Core strategy Combination therapy Single-molecule multi-agonist Pathways Amylin + GLP-1 GIP + GLP-1 + glucagon Main components Cagrilintide + semaglutide Retatrutide (LY3437943) 2026 status Phase 3 / regulatory-watch candidate Phase 3 TRIUMPH program Best-fit research question Can amylin extend GLP-1 results
![Cardiovascular disease continuum-GLP-1 action. Adapted from [46]](https://www.researchgate.net/publication/357072789/figure/fig1/AS:1146405179654167@1650335702879/Cardiovascular-disease-continuum-GLP-1-action-Adapted-from-46.png)
