Tirzepatide is a dual GIP and GLP-1 receptor agonist that has demonstrated improved glycemic control and superior weight loss. Tirzepatide induces the internalization of GIP and GLP-1 receptors in different ways, with EC50 values of 18.2 nM and 18.1 nM, respectively [1-4].
After tirzepatide treatment(10 nmol/kg; s.c.;3 or 14-days), the weight and food intake of mice were significantly reduced[5]. Chronic treatment with tirzepatide (10 nmol/kg; s.c.; 14-days) enhanced insulin tolerance in obese mice[6]. In mice and rats, treatment with tirzepatide(0.3, 1, 3, 10 and 30 nmol/kg; s.c.; 14-days) simultaneously reduced the intake of a palatable high-fat/high-sugar diet and increased the consumption of a low-fat chow diet[7].
References:
[1]. Willard FS, Douros JD, et,al. Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist. JCI Insight. 2020 Sep 3;5(17):e140532. doi: 10.1172/jci.insight.140532. PMID: 32730231; PMCID: PMC7526454.
[2].Nauck MA, D'Alessio DA. Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading glycaemic control and body weight reduction. Cardiovasc Diabetol. 2022 Sep 1;21(1):169. doi: 10.1186/s12933-022-01604-7. PMID: 36050763; PMCID: PMC9438179.
[3]. Frías JP. Tirzepatide: a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) dual agonist in development for the treatment of type 2 diabetes. Expert Rev Endocrinol Metab. 2020 Nov;15(6):379-394. doi: 10.1080/17446651.2020.1830759. Epub 2020 Oct 8. PMID: 33030356.
[4]. Frías JP, Davies MJ, et,al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021 Aug 5;385(6):503-515. doi: 10.1056/NEJMoa2107519. Epub 2021 Jun 25. PMID: 34170647.
[5]. Samms RJ, Zhang G, et,al. Tirzepatide induces a thermogenic-like amino acid signature in brown adipose tissue. Mol Metab. 2022 Oct;64:101550. doi: 10.1016/j.molmet.2022.101550. Epub 2022 Jul 31. PMID: 35921984; PMCID: PMC9396640.
[6]. Samms RJ, Christe ME, et,al. GIPR agonism mediates weight-independent insulin sensitization by tirzepatide in obese mice. J Clin Invest. 2021 Jun 15;131(12):e146353. doi: 10.1172/JCI146353. PMID: 34003802; PMCID: PMC8203452.
[7]. Geisler CE, Antonellis MP, et,al. Tirzepatide suppresses palatable food intake by selectively reducing preference for fat in rodents. Diabetes Obes Metab. 2023 Jan;25(1):56-67. doi: 10.1111/dom.14843. Epub 2022 Sep 12. PMID: 36054312; PMCID: PMC10362946.
Tirzepatide是一种双GIP和GLP-1受体激动剂，可以改善血糖控制和减轻体重。Tirzepatide以不同方式诱导GIP和GLP-1受体内化，EC50值分别为18.2 nM和18.1 nM[1-4]。
Tirzepatide治疗(10 nmol/kg; s.c.;3 or 14-days)后，小鼠体重和摄食量均显著降低[5]。Tirzepatide (10 nmol/kg; s.c.; 14-days) 慢性治疗后，可提高肥胖小鼠的胰岛素耐受性[6]。在小鼠和大鼠中，Tirzepatide治疗(0.3, 1, 3, 10 and 30 nmol/kg; s.c.; 14-days)同时减少了高脂肪/高糖饮食的摄入量，增加了低脂肪食物的摄入量[7]。