URLi (LY900014), a novel ultra-rapid mealtime insulin in Phase 3 development, is shown to reduce postprandial glucose after subcutaneous injection. This study evaluated the pharmacokinetics and pharmacodynamics (PD) of URLi via CSII. In a double-blind, randomized cross-over study, 24 adult patients with T1D received URLi or insulin lispro (Humalog®; HL) for 3 days. Mixed meal tolerance tests (MMTT) were conducted on Days 1 and 3 after catheter insertion using a standard (1.5 U/min) single-wave bolus. URLi showed faster insulin lispro absorption on both days compared to HL. URLi reduced time to early half-maximal drug concentration by 37% (-8.5 min) and 32% (-5.3 min) compared to HL on Days 1 and 3 (both p<0.0001). Area under the insulin lispro concentration time curve (AUC) for the first 15 min was >50% higher than HL after dosing with URLi on Days 1 and 3 (p<0.005). URLi reduced 1-hour postprandial glucose excursion of the MMTT by 45% on Day 1 (p=NS) and 47% on Day 3 (p=0.059) compared with HL (Figure). Accelerated URLi absorption was associated with trends toward lower postprandial glucose excursion for the entire MMTT (57% and 20% reductions in ∆AUC[0-5h] on Days 1 and 3; both NS). The study was not powered for PD assessment which may contribute to the lack of statistical significance. No differences were seen in the number or severity of hypoglycemic events or local tolerability between URLi and HL.
C.M. Kazda: Employee; Self; Eli Lilly and Company. J. Leohr: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Employee; Spouse/Partner; Accenture. Stock/Shareholder; Spouse/Partner; Accenture. R. Liu: Employee; Self; Eli Lilly and Company. Employee; Spouse/Partner; Eli Lilly and Company. T. Hardy: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. S. Reddy: None. S.P.C. Chua: Employee; Self; Eli Lilly and Company. X. Guo: None. U. Hovelmann: None. C. Kapitza: Research Support; Self; ADOCIA, Boehringer Ingelheim GmbH, Dance Biopharm, Eli Lilly and Company, Johnson & Johnson Services, Inc., MedImmune, MSD K.K., Mylan, Nordic Bioscience, Novo Nordisk Inc., Poxel SA, Roche Diagnostics Corporation, Saniona, Sanofi-Aventis, Senseonics, Zealand Pharma A/S.