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:

To compare 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).

MATERIALS AND METHODS:

This was a two-part, randomized, double-blind, Phase 1b study. Part A used a six-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 min before, immediately before, and 15 min 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-week period when insulins were administered immediately before the start of the meal.

RESULTS:

URLi increased the insulin exposure within the first 30 min postdose by 2.2-fold and reduced the time to early half-maximal drug concentration by 37% compared with Humalog. Overall, URLi resulted in better postprandial glucose lowering when dosed before, immediately before, or after a meal compared with Humalog. Comparing the same meal-to-dose timing between the insulins, postprandial glucose excursion over 5 hours was reduced by 40%-44% for all three dose timings (-15, 0, and +15 min) with URLi, achieving statistical significance for the 0- and +15-min 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 the outpatient period.

CONCLUSIONS:

URLi showed accelerated insulin lispro absorption and greater postprandial glucose reduction at different meal-to-dose timings compared with Humalog and was well tolerated in patients with T1D.

• Authors: Christof Kazda, Jennifer Leohr, Rong Liu, Shobha Reddy, Mary Anne Dellva, Mei Teng Loh, Thomas Hardy, Leona Plum-Mörschel
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 24 Issue 2 Pg. 196-203 (02 2022) ISSN: 1463-1326 [Electronic] England
• PMID: 34595812 (Publication Type: Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 Eli Lilly and Company. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Chemical References

• Blood Glucose
• Hypoglycemic Agents
• Insulin
• Insulin Lispro
• Glucose

Topics

• Blood Glucose
• Cross-Over Studies
• Diabetes Mellitus, Type 1 (drug therapy)
• Glucose (therapeutic use)
• Humans
• Hypoglycemic Agents (adverse effects)
• Insulin (therapeutic use)
• Insulin Lispro
• Postprandial Period