Retatrutide (LY3437943) is a triple agonist of the glucagon receptor, glucose-dependent insulinotropic polypeptide receptor, and glucagon-like peptide-1 receptor (GLP-1R), and inhibits GCGR, GIPR, and GLP-1R.Retatrutide can be used to study obesity.

GCGR:5.79 nM (EC50, human), GLP1R:0.775 nM (EC50, human), GIPR:2.8 nM (Ki, mouse), GIPR:0.0643 nM (EC50, human), GLP1R:7.2 nM (Ki, human), GCGR:2.32 nM (EC50, mouse), GLP1R:1.3 nM (Ki, mouse), GIPR:0.057 nM (Ki, human), GIPR:0.191 nM (EC50, mouse), GCGR:5.6 nM (Ki, human), GLP1R:0.794 nM (EC50, mouse), GCGR:73 nM (Ki, mouse)

Retatrutide (LY3437943) exhibits activity against human GCGR, GIPR, and GLP-1R with EC50 values of 5.79, 0.0643, and 0.775 nM, respectively[1].
For mouse GCGR, GIPR, and GLP-1R, Retatrutide shows activity with EC50 values of 2.32, 0.191, and 0.794 nM, respectively[1].
In terms of binding affinity, Retatrutide has Ki values of 5.6, 0.057, and 7.2 nM for human GCGR, GIPR, and GLP-1R, respectively[1].
Similarly, for mouse GCGR, GIPR, and GLP-1R, Retatrutide exhibits binding affinity with Ki values of 73, 2.8, and 1.3 nM, respectively[1].

In vivo, Retatrutide (LY3437943) engages with GCGR and, when administered through subcutaneous injection at a single dose of 0.47 mg/kg, improves glucose tolerance in an ipGTT (intraperitoneal glucose tolerance test) through activation of GIP or GLP-1 receptors[1].
With subcutaneous injections at 10 mL/kg every 3 days in a cycle sustained for 21 days, Retatrutide leads to significant weight reduction and increased energy expenditure through activation of glucagon receptor[1].