Faster Recovery from Hyperglycemia with Ultrarapid Lispro (URLi) vs. Humalog in Patients with Type 1 Diabetes (T1D) on Continuous Subcutaneous Insulin Infusion (CSII)

URLi is a novel insulin lispro formulation developed to more closely match physiological insulin secretion. This randomized, double-blind, 2-period, crossover study compared pharmacokinetics and glucodynamics of URLi vs. Humalog during recovery from hyperglycemia (plasma glucose [PG] >240 mg/dL) due to missed meal bolus or basal insulin suspension in 32 adults with T1D on CSII.Following a missed meal bolus, a correction dose of URLi reduced maximum PG (-13 mg/dL; p=0.02), produced more rapid decline in PG (23 mg/dL/hr; p=0.07), and achieved recovery (PG 140 mg/dL) 23 min earlier (p=0.1) vs. Humalog. Similar results were observed during recovery of hyperglycemia due to basal suspension: a correction dose of URLi reduced maximum PG (-6 mg/dL; p=0.02), produced faster PG decline (24 mg/dL/hr; p<0.001), and achieved recovery 16 min earlier (p=0.001) vs. Humalog.The early 50% tmax for insulin lispro occurred sooner (-6 or -12 min; p<0.001), and early insulin exposure was greater (2.5 or 4.3 fold, AUC0-15min; 1.7 or 2.5 fold AUC0-30min; both p<0.001), with URLi vs. Humalog after correction bolus for a missed meal bolus or basal insulin suspension, respectively.During episodes of hyperglycemia commonly experienced by patients with T1D, a correction dose of URLi provided faster recovery vs. Humalog, reflective of the faster insulin absorption.View largeDownload slideView largeDownload slide DisclosureJ. Leohr: None. E. S. Labell: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company, Johnson & Johnson, Novartis AG, Procter & Gamble Company. M. A. Dellva: Employee; Self; Eli Lilly and Company. Z. Tong: Employee; Self; Lilly Diabetes. J. Arrubla: None. L. Plum-moerschel: None. E. Zijlstra: Speaker’s Bureau; Self; Novo Nordisk A/S. T. Fukuda: Employee; Self; Eli Lilly and Company. T. Hardy: Employee; Self; Eli Lilly and Company. FundingEli Lilly and Company