Ultra rapid lispro lowers postprandial glucose and more closely matches normal physiological glucose response compared to other rapid insulin analogues: A phase 1 randomized, crossover study.

Abstract

AIMS:

To compare the pharmacokinetic (PK) and glucodynamic (GD) characteristics of ultra rapid lispro (URLi; Eli Lilly and Company, Indianapolis, Indiana), Fiasp® (Novo Nordisk, Bagsvaerd, Denmark), Humalog® (Eli Lilly and Company) and NovoRapid® (Novo Nordisk), in patients with type 1 diabetes (T1D).

MATERIALS AND METHODS:

This was a randomized, double-blind, four-period, crossover study, conducted in 68 patients with T1D. Patients received the same individualized subcutaneous dose of each study drug immediately prior to a liquid test meal. For comparison, 12 healthy subjects received the same test meal.

RESULTS:

URLi had a significantly faster insulin absorption compared to the other insulins tested. Early half-maximal drug concentration was reached 13 minutes after administration of URLi, which was 6 minutes faster than Fiasp, 13 minutes faster than Humalog, and 14 minutes faster than NovoRapid (all P <0.0001). Early insulin exposure was significantly greater and late insulin exposure was reduced after URLi compared to the other insulins. URLi achieved the greatest numerical reduction in postprandial glucose (PPG) at 2 hours post-meal (7 mg/dL vs Fiasp) and was significantly different from Humalog (21 mg/dL) and Novo Rapid (29 mg/dL). Additionally, glucose excursions over the first 3 hours post-meal with URLi were comparable to those in healthy subjects.

CONCLUSIONS:

URLi demonstrated the fastest insulin absorption and the greatest numeric PPG-lowering effect compared to the other insulins tested. URLi more closely matched the early physiological glucose control observed in healthy subjects.

• Authors: Tim Heise, Helle Linnebjerg, David Coutant, Elizabeth LaBell, Eric Zijlstra, Christoph Kapitza, Juliana Bue-Valleskey, Qianyi Zhang, Mary Anne Dellva, Jennifer Leohr
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 22 Issue 10 Pg. 1789-1798 (10 2020) ISSN: 1463-1326 [Electronic] England
• PMID: 32436641 (Publication Type: Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. 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
• Humans
• Hypoglycemic Agents (therapeutic use)
• Insulin
• Insulin Lispro