Tirzepatide

Tirzepatide (development code LY3298176) is a synthetic 39-residue linear peptide first characterised in the peer-reviewed literature by Coskun and colleagues in 2018 as a novel dual agonist of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors. The molecule is engineered on a GIP-based backbone with α-aminoisobutyric acid substitutions at positions 2 and 13, and a lysine-20 side chain acylation with a C20 fatty-di-acid via a γGlu-2xOEG spacer.

These modifications produce two convergent effects: resistance to dipeptidyl peptidase-4 (DPP-4) cleavage and reversible non-covalent binding to serum albumin. Together they extend the plasma half-life of Tirzepatide to approximately five days in humans, supporting once-weekly subcutaneous dosing.

Reported in-vitro pharmacology characterises Tirzepatide as animbalanced dual agonist — it retains near-native potency at the GIP receptor while showing reduced β-arrestin recruitment at the GLP-1 receptor relative to native GLP-1 — a form of biased agonism. Human outcome trials to date include the SURPASS programme in type 2 diabetes and the SURMOUNT programme in obesity.

Oxford Research Peptides supplies Tirzepatide strictly as a reference standard for in-vitro laboratory research. Nothing on this page constitutes medical advice or endorses any therapeutic use of research-grade material. Approved Tirzepatide medicines (Mounjaro, Zepbound) are prescribed by qualified clinicians under MHRA authorisation.

Tirzepatide is a 39-residue linear peptide with one lysine side-chain modification and no disulfide bonds. Its backbone is derived from GIP rather than GLP-1, distinguishing it structurally from the GLP-1 analogue class (Liraglutide, Semaglutide) and from the triple agonist Retatrutide.

Tirzepatide simultaneously agonises the GIP receptor and the GLP-1 receptor. Reported in-vitro pharmacology characterises it as an imbalanced dual agonist: near-native potency at GIPR with reduced β-arrestin recruitment at GLP-1R relative to native GLP-1. Both receptors are class B (secretin-family) GPCRs coupled predominantly to Gαs.

• GIP receptor agonism: Reproduces GIP-like Gαs / cAMP / PKA signalling in β-cells and adipocytes. GIP signalling supports glucose-dependent insulin exocytosis in islets and modulates adipocyte lipid handling.
• GLP-1 receptor agonism (biased): Engages Gαs coupling and cAMP elevation while recruiting less β-arrestin than native GLP-1 at matched receptor occupancy. This biased profile is one hypothesised contributor to Tirzepatide's differentiated pharmacology.
• Dual incretin biology: Concurrent GIP and GLP-1 receptor engagement leverages two parallel incretin pathways whose actions on β-cells, α-cells and central appetite circuits are complementary rather than redundant.
• Central appetite modulation: Both GIP and GLP-1 receptors are expressed in hypothalamic and hindbrain populations that integrate satiety signalling; the dual engagement is proposed to broaden central coverage relative to mono-agonists.

Two structural features drive Tirzepatide's pharmacokinetics: DPP-4 resistance conferred by Aib substitutions at positions 2 and 13, and albumin binding conferred by a C20 fatty-di-acid attached at lysine-20 through a γGlu-2xOEG linker.

• Plasma half-life (human): approximately 5 days after subcutaneous administration.
• Steady state: achieved after 4 weeks of once-weekly dosing (5 half-lives).
• Bioavailability (SC): ~80% of the injected dose.
• Protein binding: ~99% (predominantly albumin).
• Elimination: primarily proteolytic; renal and biliary excretion of small peptide fragments.

Tirzepatide reference standards are supplied lyophilised. As with other long-chain acylated peptides, careful aseptic technique, low-binding plasticware and awareness of surface adsorption at low concentrations are essential.

Reconstitute per the laboratory SOP. A general procedure is documented in the Laboratory Reconstitution Guide. The summary below applies to Tirzepatide as a long-chain acylated peptide:

1. Equilibrate the sealed vial to room temperature.
2. Introduce sterile or bacteriostatic water slowly against the vial wall.
3. Swirl gently — do not vortex — to protect the peptide backbone.
4. Allow complete dissolution; a faint opalescence at high concentration is consistent with the surface-active fatty-di-acid side chain.
5. Aliquot into low-binding vials; label with peptide, concentration, batch, date and analyst.