Verifying the Safety of Microbial Contamination in Self-Injectors of Glucagon-like peptide-1 Receptor Agonists

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) enhance insulin secretion in patients with type 2 diabetes mellitus in a glucose concentration-dependent manner. Many GLP-1RA formulations are administered in divided doses using a needle attached to the patient. Prior to use, the formulation is store in a cool place owing to stability. However, it is store at room temperature after use owing to problems with the injector. Therefore, the split-dose GLP-1RAs formulations contain phenolic antiseptics (phenol and cresol). Contamination of the formulation with microorganisms must be considered because patient self-injection is not performed under aseptic conditions. Therefore, this study verified the safety against microbial contamination during use based on Escherichia coli survival in split-dose GLP-1RA formulations. Unused liraglutide, exenatide, and lixisenatide were contaminated with E. coli stored at 25°C (room temperature) and cultured over time. E. coli gradually decreased immediately after suspension and E. coli did not survive after 60-90 min. The preservative of the split-dose GLP-1RAs formulation exhibited sufficient sterilizing power at 25°C, and it was inferred that room temperature is preferable for storage after use considering the formulation storage conditions, including injector failure and drug denaturation.