What Is Tirzepatide?

Tirzepatide (also known as LY3298176) is a first-in-class, synthetic 39-amino acid linear peptide engineered as a single-molecule dual agonist for both the glucose-dependent insulinotropic polypeptide (GIP) receptor and the glucagon-like peptide-1 (GLP-1) receptor. [1] Developed by Eli Lilly and Company, this “twincretin” approach harnesses the synergistic effects of targeting both incretin pathways simultaneously. [2]

The peptide is based on the native GIP sequence, modified with α-aminoisobutyric acid (Aib) residues at positions 2 and 13 for DPP-4 resistance, and a C20 fatty diacid moiety (eicosanedioic acid) attached via a hydrophilic linker to the lysine residue at position 20 to promote albumin binding (≥99%), yielding an approximately 5-day half-life (116.7 hours) enabling convenient once-weekly dosing. [3]

Tirzepatide functions as an imbalanced agonist — it exhibits binding affinity for the GIP receptor equivalent to native GIP, but approximately 5- to 13-fold weaker affinity for the GLP-1 receptor compared to native GLP-1. [6] Despite this imbalance, the dual mechanism produces superior outcomes across multiple clinical endpoints compared to selective GLP-1 receptor agonists. [7]

Tirzepatide has been approved by the FDA under the brand names Mounjaro® (type 2 diabetes, May 2022) and Zepbound® (chronic weight management, Nov 2023; obstructive sleep apnea, Dec 2024), and by the EMA for type 2 diabetes and weight management. [4] It is listed on the WADA Prohibited List under section S2 (Peptide Hormones, Growth Factors, Related Substances, and Mimetics). It is supplied as a sterile, preservative-free solution for subcutaneous injection — note that this product is not a lyophilized powder. [5]