Ultra Rapid Lispro (URLi) Reduces Postprandial Glucose Excursions vs. Humalog® in Patients with T1D 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.

Materials:

This 2-part, randomized, double-blind, Phase 1b study evaluated the differences in PK and PD between URLi and insulin lispro (Humalog®; HL) in 30 patients with T1D. Part A used a 6 period crossover design to evaluate 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 the 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 MMMT regardless of dose timing. URLi reduced ΔAUC0 – 2h by 103% (p = 0.008), 39% (p = 0.031), and 16% (p = 0.096), and ΔAUC0 – 5h by 40% (p = NS), 44% (p = 0.097), and 42% (p = 0.026) 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). Similar number of hypoglycemic events occurred between treatments during MMTTs. During 2 wks of outpatient dosing, the number of events was lower for URLi vs. HL. Local tolerability was similar between treatments.

Conclusion:

URLi has shown consistent reductions in postprandial glucose excursions vs. HL irrespective of the injection-meal