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Regulatory Milestones 2022 (May) : FDA approval of Mounjaro for type 2 diabetes (5, 10, 15 mg doses) 2023 (November) : FDA approval of Zepbound for chronic weight management (same molecule, obesity-specific branding) 2024 : EMA approval in European Union for both indications 2025 : SURPASS-CVOT cardiovascular outcomes data published, showing MACE benefit Molecular Structure and Chemistry Amino Acid Sequence Tirzepatide is a 39-amino acid peptide based on native human GIP(1-42) with multiple modifications: Modified sequence : Tyr-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-Leu-Asp-Lys-Ile-Ala-Gln-Lys-Lys*(C-20 diacid via Glu-2xOEG)-Ala-Phe-Val-Gln-Trp-Leu-Ile-Ala-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH 2 Single-letter code : Y- Aib -E-G-T-F-T-S-D-Y-S-I- L -D-K-I-A-Q- K K *- A -F-V-Q-W-L-I-A-G-G-P-S-S-G-A-P-P-P-S-NH 2 Where bold indicates non-native substitutions vs

4 Nutritional antagonism: interaction of other amino acids with arginine A dietary balance of micronutrients, such as essential amino acids, is important for optimum growth and development (Zampiga et al., 2018)

For instance, NPs stabilized by electrostatic double layer repulsions tend to aggregate when an excess of counterionic residues is introduced

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