Trizepatide

Tirzepatide Overview

Tirzepatide (LY3298176) is a synthetic 39-amino acid peptide and first-in-class dual GIP and GLP-1 receptor agonist, often referred to as a twincretin. It was engineered by building GLP-1 activity into the native GIP peptide sequence, resulting in a compound that simultaneously activates both incretin hormone receptors. GLP-1 activation suppresses appetite, delays gastric emptying, and stimulates glucose-dependent insulin secretion, while GIP augments that insulin response and modulates adipose tissue metabolism. The synergistic effect of both pathways produces greater glycemic control and weight reduction than either mechanism alone.

History

Tirzepatide was developed by Eli Lilly and Company from earlier preclinical research into dual incretin co-agonism through the 2010s. The SURPASS phase 3 clinical trial program confirmed its safety and efficacy across five large trials. It received FDA approval on May 13, 2022, for the treatment of type 2 diabetes and subsequently received approval for obesity treatment under the brand name Zepbound. It remains available as a research compound for in-vitro metabolic pathway studies.

Key Studies

1. Frias JP, et al. — Phase 2 discovery and proof of concept (2018) Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes. The Lancet. → https://pubmed.ncbi.nlm.nih.gov/30293771/
2. Rosenstock J, et al. — SURPASS-1 Phase 3 trial (2021) Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes. The Lancet. → https://pubmed.ncbi.nlm.nih.gov/34186022/
3. Jastreboff AM, et al. — SURMOUNT-1 obesity trial (2022) Tirzepatide once weekly for the treatment of obesity. New England Journal of Medicine. → https://pubmed.ncbi.nlm.nih.gov/35658024/