Ultra Rapid Lispro (URLi) Shows Accelerated Pharmacokinetics and Greater Reduction in Postprandial Glucose versus Humalog® in Patients with Type 1 Diabetes Mellitus in a Randomized, Double-blind Meal Test Early Phase Study.

Abstract

AIM\nThis study compared the pharmacokinetics (PK), glucodynamics (GD), and tolerability following single and multiple daily subcutaneous (SC) doses of ultra rapid lispro (URLi) and Humalog in patients with type 1 diabetes mellitus (T1D).\n\n\nMATERIALS AND METHODS\nThis was a 2-part, randomized, double-blind, Phase 1b study. Part A used a 6-period crossover design to assess PK and GD response to a solid mixed meal tolerance test (MMTT) following a single dose of URLi or Humalog administered 15 minutes before, immediately before, and 15 minutes after the start of the meal. Part B evaluated URLi or Humalog during 2-weeks of multiple daily dosing with a parallel design. The PK and GD were assessed following MMTTs at the beginning and end of the 2-weeks when insulins were administered immediately before the start of the meal.\n\n\nRESULTS\nURLi increased the insulin exposure within the first 30-minutes post-dose by 2.2-fold and reduced the time to early half-maximal drug concentration by 37% compared to Humalog. Overall, URLi resulted in better postprandial glucose lowering when dosed before, immediately before, or after a meal compared to Humalog. In comparing the same meal-to-dose timing between the insulins, the postprandial glucose excursion over 5 hours was reduced by 40-44% for all 3 dose timings (-15 minutes, 0 minutes, and +15 minutes) with URLi, achieving statistical significance for the 0- and +15-minute timings. The PK and GD profiles were sustained after daily SC dosing for 2-weeks in patients with T1D. The number of documented hypoglycaemic events was similar between URLi and Humalog during the postprandial period of the MMTTs and outpatient period.\n\n\nCONCLUSIONS\nURLi demonstrated an accelerated insulin lispro absorption and greater postprandial glucose reduction at different meal-to-dose timings compared to Humalog and was well tolerated in patients with T1D. This article is protected by copyright. All rights reserved.