Ultra-rapid lispro shows faster pharmacokinetics and reduces postprandial glucose excursions versus Humalog® in patients with type 2 diabetes mellitus in a randomized, controlled crossover meal test early phase study.

Abstract

AIMS:

To compare the pharmacokinetics (PK), glucodynamics (GD) and tolerability following single and multiple daily subcutaneous doses of ultra rapid lispro (URLi) and Humalog® in patients with type 2 diabetes mellitus (T2D).

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 minutes before, immediately before, or 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.

RESULTS:

URLi increased the insulin exposure within the first 30 minutes postdose by 2.2-fold and reduced the time to the early half-maximal drug concentration by 22.6% compared with Humalog. Overall, URLi resulted in better postprandial glucose lowering when dosed before, immediately before, or after a meal. In comparing the same meal-to-dose timing between the insulins, the postprandial glucose excursion over 5 hours was significantly reduced by 29%-105% for all three dose timings (-15, 0 and +15 minutes) with URLi. The PK and GD were sustained after daily subcutaneous dosing for 2 weeks in patients with T2D. URLi had more hypoglycaemic events during the MMTTs; few events occurred for both treatments during the 2 weeks of outpatient dosing.

CONCLUSIONS:

URLi demonstrated 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 T2D.

• Authors: Jennifer Leohr, Christof Kazda, Rong Liu, Shobha Reddy, Mary Anne Dellva, Mark Matzopoulos, Mei Teng Loh, Thomas Hardy, Oliver Klein, Christoph Kapitza
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 24 Issue 2 Pg. 187-195 (02 2022) ISSN: 1463-1326 [Electronic] England
• PMID: 34605142 (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)
• Diabetes Mellitus, Type 2 (chemically induced, drug therapy)
• Glucose (therapeutic use)
• Humans
• Hypoglycemic Agents (adverse effects)
• Insulin (therapeutic use)
• Insulin Lispro
• Postprandial Period