Tirzepatide is an agonist of glucagon-like peptide 1 receptor (GLP-1R) and gastric inhibitory polypeptide (GIP) receptor.[1] It induces cAMP production in HEK293 cells expressing human GLP-1R or human GIP receptor (EC50s = 6.54 and 1.01 nM, respectively). Tirzepatide (100 nM) induces receptor internalization in HEK293 cells expressing human GLP-1R or GIP receptor. In vivo, tirzepatide (10 nmol/kg per day) decreases body weight, food intake, plasma levels of leptin, triglycerides, and free fatty acids (FFAs), hepatic levels of triglycerides, and blood glucose levels in a mouse model of high-fat diet-induced obesity.[2] It prevents A. alternata-induced increases in the numbers of eosinophils and lymphocytes in the bronchoalveolar lavage fluid (BALF) from A. alternata-challenged mice when administered at a dose of 50 nmol/kg every three days.[3] Tirzepatide (50 nmol/kg every three days) inhibits bronchoconstriction induced by the muscarinic receptor agonist methacholine (acetyl-β-methylcholine; ) in a mouse model of diabetes-induced asthma. Formulations containing tirzepatide have been used in the treatment of type 2 diabetes mellitus.
References:
[1].Willard, F.S., Douros, J.D., Gabe, M.B.N., et al.Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonistJCI Insight5(17)e140532(2020).
[2].Samms, R.J., Christe, M.E., Collins, K.A.L., et al.GIPR agonism mediates weight-independent insulin sensitization by tirzepatide in obese miceJ. Clin. Invest.131(12)e146353(2021).
[3].Toki, S., Zhang, J., Printz, R.L., et al.Dual GIPR and GLP-1R agonist tirzepatide inhibits aeroallergen-induced allergic airway inflammation in mouse model of obese asthmaClin. Exp. Allergy53(2)216-221(2023).