Diabetologie und Stoffwechsel 2016; 11 - P250
DOI: 10.1055/s-0036-1580997

The in vitro pharmacology of LY IGlar (LY2963016): A new insulin glargine product

RA Owens 1, SD Kahl 1, X Ruan 1, C Zhang 1, MW Farmen 1, JS Moyers 1, MD Michael 1
  • 1Eli Lilly and Company, Indianapolis, United States

Objective: Basal insulin analogs, with durations of action sufficient for coverage over the course of 24h, are important for the proper management of glycemic control in diabetic patients. LY2963016 (LY IGlar), an insulin analog has the same amino acid sequence as Lantus® (IGlar). The pharmacological properties of six independent lots of LY IGlar and IGlar were compared using a panel of in vitro biological assays to determine the pharmacological similarity of LY IGlar compared to IGlar.

Methods: The affinity, Ki, for the human insulin receptor isoform A (hIR-A) and B (hIR-B) and human IGF-1 receptor (hIGF-1R) and the half-maximal concentration, EC50, required to stimulate phosphorylation were determined using competitive receptor binding assays. Statistical comparisons were made for the Ki/EC50 responses from each assay using the Sidak and Holm-Bonferroni multiple comparison adjustment methods with α= 0.05.

Results: Ki of LY IGlar was 0.41 ± 0.01, 0.45 ± 0.03, and 16.0 ± 0.4 nM for hIR-A, hIR-B, and hIGF-1R, respectively. These affinities were comparable to the Ki of IGlar, 0.40 ± 0.02, 0.45 ± 0.04, and 15.5 ± 0.6 nM, respectively. The EC50 of LY IGlar required to stimulate hIR-A and hIR-B phosphorylation was similar to the EC50 for IGlar. LY IGlar and IGlar were maximally efficacious with comparable EC50 concentrations for stimulating de novo lipogenesis from glucose. The mitogenic potential of LY IGlar and IGlar in the hIGF-1R dominant cell line, Saos-2, was 0.53 ± 0.03 and 0.53 ± 0.03 nM, respectively.

Conclusions: The in vitro pharmacological properties of LY IGlar were not significantly different from IGlar, thus supporting LY IGlar as an alternative therapy for diabetic patients.