Insulin Glargine and Insulin Aspart Overdose With Pharmacokinetic Analysis

ABSTRACT Objective: Insulin glargine is a long-acting insulin analogue with biotransformation, at the injection site, to a primary active metabolite (glargine-M1). Combined therapy with rapid-acting insulin aspart is common, but pharmacokinetics with supra-therapeutic doses have not been reported. We present clinical and pharmacokinetic findings for 2 episodes of overdose with glargine and aspart in a 43-year-old male with type 1 diabetes. Methods: Liquid chromatography–tandem mass spectrometry was used to detect and quantitate the M1 and insulin aspart levels in the serum of an individual who administered large supra-therapeutic doses of these medications. Results: Prolonged insulin analogue action was associated with measurable aspart levels in the circulation for the first day and with glargine-M1 for up to 5 days. Dextrose infusion rate correlated closely with the circulating levels of aspart and glargine-M1. Throughout the clinical treatment, glargine concentrations were near or below the threshold of detection. Several peaks of glargine metabolite were observed before it was completely undetectable. The pharmacokinetic profile of the simultaneous insulin aspart overdose was also prolonged. Conclusion: This is the first report of a simultaneous overdose in insulin glargine and insulin aspart where direct serum measurements were made of insulin glargine, its active metabolite glargine-M1, and insulin aspart. This case demonstrates a substantial contribution of glargine-M1 to the severity and prolongation of hypoglycemic risk in glargine overdose. Abbreviations: Glargine-M1 = active metabolite glargine-M1 IV = intravenous LC-MS/MS = liquid chromatography–tandem mass spectrometry LOQ = limit of quantification