Cobalt PeptidesResearch Grade

Scientific Reference

Tirzepatide

Evidence profile: Human Phase 3 evidence

Tirzepatide is a synthetic 39-residue peptide that activates two incretin receptors, the GIP receptor and the GLP-1 receptor. Its backbone is modelled on glucose-dependent insulinotropic polypeptide (GIP), with aminoisobutyric acid at positions 2 and 13 and a C-terminal segment resembling that of exendin-4. A 20-carbon fatty diacid, attached to a lysine through a linker, binds albumin and extends its time in circulation. Beyond receptor pharmacology and rodent work, it has a large human clinical literature in metabolic disease. What the GIP component contributes is still debated, partly because rodent studies have reported overlapping effects from both activating and blocking the GIP receptor.

Mechanism of Action

Tirzepatide has been reported to bind and activate both the GIP receptor and the GLP-1 receptor, class B G-protein-coupled receptors that signal chiefly through Gs and cyclic AMP. In vitro, its affinity at the GIP receptor is described as similar to that of native GIP, while at the GLP-1 receptor it is weaker than native GLP-1, so it is often called an imbalanced agonist. At the GLP-1 receptor it has also been reported to favour cyclic AMP generation over β-arrestin recruitment, with less receptor internalisation. GIP receptors occur in pancreatic islets, adipose tissue and the brain; GLP-1 receptors occur in islets, the gut and brain regions linked to feeding.

Molecular Information

  • Type: Dual GIP/GLP-1 receptor agonist
  • Length: 39 amino acids
  • Molecular weight: 4813 g/mol
  • Molecular formula: C225H348N48O68
  • CAS: 2023788-19-2

Pharmacokinetics

The apparent population mean clearance of tirzepatide is 0.061 L/h with an elimination half-life of approximately 5 days, enabling once-weekly dosing. Table 2, normal hepatic function group: "t max , h: 24.00 (8.00-72.00)" reported as median (range) following a single 5-mg subcutaneous dose (n=13).

Published Research

  • SURMOUNT-5

    Tirzepatide as Compared with Semaglutide for the Treatment of Obesity

    Aronne LJ et al. · The New England journal of medicine · 2025 · Clinical

    PMID 40353578 — View on PubMed

  • SURMOUNT-1

    Tirzepatide Once Weekly for the Treatment of Obesity

    Jastreboff AM et al. · The New England journal of medicine · 2022 · Clinical

    PMID 35658024 — View on PubMed

  • SURPASS-2

    Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes

    Frías JP et al. · The New England journal of medicine · 2021 · Clinical

    PMID 34170647 — View on PubMed

  • Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist

    Willard FS et al. · JCI insight · 2020 · Preclinical

    PMID 32730231 — View on PubMed

  • Tirzepatide for maintenance of bodyweight reduction in people with obesity in the USA (SURMOUNT-MAINTAIN): a multicentre, double-blind, randomised, placebo-controlled trial

    Horn DB et al. · Lancet (London, England) · 2026 · Clinical

    PMID 42119587 — View on PubMed

  • Efficacy and safety of tirzepatide in children and adolescents with type 2 diabetes (SURPASS-PEDS): a randomised, double-blind, placebo-controlled, phase 3 trial

    Hannon TS et al. · Lancet (London, England) · 2025 · Clinical

    PMID 40975112 — View on PubMed