URLi (LY900014), a novel ultra-rapid mealtime insulin in Phase 3 development, is shown to reduce postprandial glucose after subcutaneous injection. This 2-part, randomized, double-blind, Phase 1b study evaluated differences in PK and PD between URLi and insulin lispro (Humalog®; HL) in 30 patients with T2D. Part A used a 6-period crossover design to assess safety and compare PK and postprandial glucose response to solid mixed meal tolerance tests (MMTT) with URLi or HL at different injection to mealtime intervals (-15, 0 and +15 min). Part B evaluated safety, PK and PD during 2 weeks of multiple daily dosing (immediately before a meal) in a parallel design.In Part A, URLi reduced glucose excursions (assessed as change in area under the concentration curve vs. time [∆AUC]) during the first 2 hours (∆AUC0-2h) and entire 5 hours (∆AUC0´5h) of the MMTT regardless of dose timing (Fig). URLi reduced ∆AUC0-2h by 37% (p=0.014), 47% (p<0.0001), and 4% (p=NS) and ∆AUC0-5h by 49% (p=0.049), 105% (p<0.0001), and 29% (p=0.076) vs. HL at ´15, 0 and +15 min (significance level =0.1). The PK and PD profiles for URLi and HL were sustained after 2 weeks of outpatient dosing (Part B). More hypoglycemic events occurred with URLi during MMTTs but these were mild and mostly asymptomatic. Only a few events occurred in either group during 2 weeks of outpatient dosing. Local tolerability was similar between treatments.
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. 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. S. Reddy: None. M.A. Dellva: Employee; Self; Eli Lilly and Company. M. Matzopoulos: None. M.P. Knadler: Other Relationship; Self; Eli Lilly and Company. M. Loh: Employee; Self; Eli Lilly and Company. T. Hardy: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. C.M. Kazda: Employee; Self; Eli Lilly and Company.