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 PubMedSURMOUNT-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 PubMedSURPASS-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 PubMedTirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist
Willard FS et al. · JCI insight · 2020 · Preclinical
PMID 32730231 — View on PubMedTirzepatide 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 PubMedEfficacy 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