Ultra Rapid Lispro (URLi) Reduces Postprandial Glucose Excursions vs. Humalog® in Patients with T2D at Multiple Meal-to-Dose Timing Intervals

Introduction:

URLi (LY900014), a novel ultra-rapid mealtime insulin in Phase 3 development, is shown to reduce postprandial glucose after subcutaneous injection.

Methods:

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 & +15 min). Part B evaluated safety, PK and PD during 2 wks of multiple daily dosing (immediately before a meal) in a parallel design.

Results:

In Part A, URLi reduced glucose excursions (assessed as change in area under the concentration curve vs. time [ΔAUC]) during the first 2 hrs (ΔAUC0 – 2h) and entire 5 hrs (ΔAUC0 5h) of the MMTT regardless of dose timing. URLi reduced ΔAUC0 – 2h by 37% (p = 0.014), 47%(p < 0.0001), and 4%(p = NS) and ΔAUC0 – 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 wks 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 wks of outpatient dosing. Local tolerability was similar between treatments.

Conclusion:

URLi shows consistent reductions in postprandial glucose excursions vs. HL irrespective of the injection-meal interval and