What Is Tirzepatide?
Tirzepatide is a synthetic 39-amino acid dual agonist peptide that activates both the GLP-1 receptor (GLP-1R) and the glucose-dependent insulinotropic polypeptide receptor (GIPR) with equal potency. Developed by Eli Lilly, it is approved by the FDA under the brand names Mounjaro (type 2 diabetes, 2022) and Zepbound (chronic weight management, 2023).
Its unique dual-agonism distinguishes it from semaglutide (pure GLP-1R agonist) and makes it the direct predecessor of Eli Lilly's triple-agonist retatrutide.
Mechanism of Action
| Receptor | Effect | |---|---| | GLP-1R | Appetite suppression, slowed gastric emptying, glucose-dependent insulin secretion | | GIPR | Enhanced insulin secretion, adipose lipid clearance, possible direct CNS appetite effects |
The GIPR component was historically controversial — GIPR agonism was expected to worsen obesity based on animal data, but clinical results demonstrated the opposite, suggesting species differences in GIPR function in adipose tissue.
SURMOUNT Clinical Trial Data
| Trial | Population | Weight Reduction | |---|---|---| | SURMOUNT-1 | Non-diabetic obese | 22.5% (15 mg, 72 weeks) | | SURMOUNT-2 | T2D obese | 15.7% (15 mg, 72 weeks) | | SURPASS-2 vs Semaglutide | T2D | Superior to sema 1 mg |
Research Applications
Beyond weight loss and T2D, active research programmes explore tirzepatide in:
- MASLD / NASH (liver disease)
- Heart failure with preserved ejection fraction (HFpEF) — SUMMIT trial
- Obstructive sleep apnoea — SURMOUNT-OSA trial (positive Phase III)
- Polycystic ovary syndrome (PCOS)
Related compounds: Semaglutide, Retatrutide, AOD-9604.