Tirzepatide (LY3298176) is a synthetic 39 amino acid peptide developed by Eli Lilly that functions as a dual agonist at both GIPR and GLP-1R. Based on the native GIP sequence with C18 fatty diacid modification at lysine 20, its half-life is approximately 5 days. Tirzepatide received FDA approval in 2022 (Mounjaro) and 2023 (Zepbound) for specific clinical indications.
Dual Incretin Receptor Pharmacology Research
Research has extensively examined tirzepatide's differential activity at GIPR versus GLP-1R and the mechanisms underlying its enhanced metabolic effects relative to selective GLP-1R agonists, including binding affinities and downstream signaling profiles.
Glucose Homeostasis and Insulin Secretion Research
Clinical and preclinical research has examined tirzepatide's effects on glucose-stimulated insulin secretion through dual incretin receptor engagement. The SURPASS clinical trial program has generated extensive clinical data on its glucose-lowering mechanisms.
GIP Receptor Biology Research
Tirzepatide has served as an important research tool for advancing understanding of GIPR biology and its role in metabolic regulation, contributing to resolving scientific debate about GIPR agonism effects when combined with GLP-1R agonism.
• Frias JP et al. (2021). Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. New England Journal of Medicine, 385(6), 503–515.
• Jastreboff AM et al. (2022). Tirzepatide once weekly for the treatment of obesity. New England Journal of Medicine, 387(3), 205–216.
