Abasaglar® (insulin glargin): Cancerframkallande och Fertilitetsnedsättande förmåga

Preclinical Safety Data

Nonclinical data for insulin glargine reveal no special hazard for humans based on

• conventional studies of safety pharmacology

• repeated dose toxicity

• genotoxicity

• carcinogenic potential, and

• toxicity to reproduction.¹

Carcinogenesis, Mutagenesis, and Impairment of Fertility With Insulin Glargine

In mice and rats, standard 2-year carcinogenicity studies with another IGlar product were performed at doses up to 0.455 mg/kg, which was for the mouse approximately 5 times and for the rat approximately 10 times the recommended human SC starting dose of 10 units/day (0.008 mg/kg/day), based on mg/m².²

The findings in female mice were not conclusive due to excessive mortality in all dose groups during the study. Histiocytomas were found at injection sites in male mice (not statistically significant) and male rats (statistically significant) in acid-vehicle containing groups. These tumors were not found in

• female animals

• saline controls, or

• insulin comparator groups using a different vehicle.²

The relevance of these findings to humans is unknown.²

Another IGlar product was not mutagenic in tests for detection of

• gene mutations in bacteria and mammalian cells (Ames and HGPRT test), and

• chromosomal aberrations (cytogenetics in vitro in V79 cells and in vivo in Chinese hamsters).²

In a combined fertility and prenatal and postnatal study of another IGlar product in male and female rats at SC doses up to 0.36 mg/kg/day, which was approximately 7 times the recommended human SC starting dose of 10 units/day (0.008 mg/kg/day), based on mg/m², maternal toxicity due to dose-dependent hypoglycemia, including some deaths, was observed. Consequently, a reduction of the rearing rate occurred in the high-dose group only. Similar effects were observed with NPH insulin.²

References

1. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

2. Basaglar [package insert]. Indianapolis, IN: Eli Lilly and Company; 2018.

Glossary

Abasaglar = Abasaglar® (insulin glargine) 100 units/mL

HGPRT = hypoxanthine-guanine phosphoribosyltransferase

IGlar = insulin glargine

SC = subcutaneous