Insulin efsitora alfa (LY-3209590) is a selective insulin receptor (IR) agonist and fusion protein that combines a novel single-chain insulin variant with the structural domain of human IgG Fc for the study of type 2 diabetes.

insulin receptor isoform A (human, IR-A):4241 nM (EC50), SAOS-2 cells:134 nM (EC50), insulin receptor subtype B (human, IR-B ):391 nM (EC50), H4IIE cells:20 nM (EC50)

Insulin efsitora alfa stimulated the phosphorylation of human insulin receptor isoform A (hIR-A) and human insulin receptor subtype B (hIR-B) in HEK293 cells at concentrations ranging from 0.01 to 100 nM with EC50 values of 4241 nM and 391 nM, respectively. hIR-A and hIR-B were significantly dephosphorylated when treated with 20 µM for 30 min. Insulin efsitora alfa significantly promoted the dephosphorylation of hIR-A and hIR-B when treated at a concentration of 20 µM for 30 min. In addition, Insulin efsitora alfa stimulated lipogenesis in 3T3-L1 adipocytes as well as proliferation of SAOS-2 and H4IIE cells with EC50 values of 19 nM, 134 nM and 20 nM, respectively. [1]

In streptozotocin -treated diabetic rats, a single subcutaneous injection of Insulin efsitora alfa (3, 10, and 30 nmol/kg) significantly reduced blood glucose levels. [1]