CEDAR

Scientific Reference

Tirzepatide

Evidence profile: Human Phase 3 evidence

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist approved for type 2 diabetes and chronic weight management. It produces significant weight loss and metabolic improvements by targeting multiple incretin pathways simultaneously. By mimicking endogenous incretin hormones, tirzepatide enhances insulin secretion, suppresses glucagon, slows gastric emptying, and reduces appetite. Clinical trials have demonstrated substantial reductions in body weight and improvements in glycaemic control, exceeding those seen with GLP-1-only therapies.

Mechanism of Action

Tirzepatide acts as a dual agonist at GIP and GLP-1 receptors. GLP-1 receptor activation suppresses appetite, delays gastric emptying, and enhances insulin secretion, while GIP receptor activation improves insulin sensitivity and metabolic regulation. The combined incretin activity produces synergistic effects on glucose control and weight reduction.

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