Tirzepatide is the first-in-class dual GIP/GLP-1 receptor co-agonist — a "twincretin" that simultaneously activates both gastrointestinal incretin hormone receptors. Its clinical data in SURMOUNT-1 represents the most significant weight reduction ever demonstrated in a Phase 3 trial at the time of publication.
What is Tirzepatide?
Tirzepatide (LY3298176) is a 39-amino-acid linear peptide engineered by Eli Lilly. It is a synthetic co-agonist of the glucose-dependent insulinotropic polypeptide (GIP) receptor and the glucagon-like peptide-1 (GLP-1) receptor, modified from native GIP with a C20 fatty diacid chain that confers an approximately 5-day half-life for once-weekly dosing in clinical protocols.
Known Mechanism of Action
GIP Receptor Activation
Tirzepatide activates the GIP receptor with approximately equal potency to native GIP. GIPR activation has insulinotropic effects at physiological glucose levels, promotes adipose tissue lipid buffering, and may increase energy expenditure. Recent research suggests GIP receptor signalling in the brain may contribute to appetite regulation and body weight modulation.
GLP-1 Receptor Activation
Tirzepatide activates the GLP-1 receptor, producing glucose-dependent insulin secretion, glucagon suppression, delayed gastric emptying, and central appetite suppression. The GLP-1 component accounts for the majority of Tirzepatide's satiety effects.
Dual Incretin Synergy
Simultaneous GIPR and GLP1R activation produces effects exceeding pure GLP-1 agonism. Proposed mechanisms include complementary receptor localisation throughout the brain and periphery, GIP-mediated enhancement of GLP-1 sensitivity, and differential effects on lipid metabolism and energy expenditure.
Clinical Trial Landmarks
- SURMOUNT-1 (N=2,539): 72-week trial — 22.5% body weight reduction at 15 mg/week vs 2.4% placebo.
- SURPASS-2 (N=1,879): A1c reduction of 2.37% at 15 mg/week — superior to semaglutide 1 mg.
- SURMOUNT-3 and -4: Demonstrate sustained weight reduction through 84 and 88 weeks.
This article is for scientific and educational purposes only. Tirzepatide is available exclusively for laboratory research.
Element42 Peptides — Australian owned, third-party tested. View Tirzepatide product page.