Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 12/2020

Open Access 01-12-2020 | Pharmacokinetics | Original Research Article

Pharmacokinetics and Glucodynamics of Ultra Rapid Lispro (URLi) versus Humalog® (Lispro) in Younger Adults and Elderly Patients with Type 1 Diabetes Mellitus: A Randomised Controlled Trial

Authors: Helle Linnebjerg, Qianyi Zhang, Elizabeth LaBell, Mary Anne Dellva, David E. Coutant, Ulrike Hövelmann, Leona Plum-Mörschel, Theresa Herbrand, Jennifer Leohr

Published in: Clinical Pharmacokinetics | Issue 12/2020

Login to get access

Abstract

Background

Ultra rapid lispro (URLi) is a novel insulin lispro formulation developed to more closely match physiological insulin secretion and improve postprandial glucose control. This study compared the pharmacokinetics, glucodynamics, safety, and tolerability of URLi and Humalog® in patients with type 1 diabetes mellitus (T1DM).

Methods

This was a phase I, two-period, randomised, double-blind, crossover glucose clamp study in younger adult (aged 18–45 years; n = 41) and elderly (aged ≥65 years; n = 39) patients with T1DM. At each dosing visit, patients received either URLi or Humalog (15 units subcutaneously) followed by a 10 h automated euglycaemic clamp procedure. Serum insulin lispro and blood glucose were measured.

Results

Insulin lispro appeared in serum 6 min faster, and exposure was 7.2-fold greater over the first 15 min postdose with URLi versus Humalog in both age groups. Exposure beyond 3 h postdose was 39–41% lower, and exposure duration was reduced by 72–74 min with URLi versus Humalog in both age groups. Onset of insulin action was 11–12 min faster, and insulin action was 3-fold greater over the first 30 min postdose with URLi versus Humalog in both age groups. Insulin action beyond 4 h postdose was 44–54% lower, and duration of action was reduced by 34–44 min with URLi versus Humalog in both age groups. Overall exposure and total insulin action remained similar for both treatments. URLi and Humalog were well tolerated.

Conclusion

In patients with T1DM, URLi showed ultra-rapid pharmacokinetics and glucodynamics, with the differences between URLi and Humalog in elderly patients mirroring those in younger adults.
ClinicalTrials.gov identifier: NCT03166124.
Appendix
Available only for authorised users
Literature
1.
American Diabetes Association. Standards of medical care in diabetes – 2013. Diabetes Care. 2013;36(Suppl 1):S11–66.CrossRef
2.
Senior P, Hramiak I. Fast-acting insulin aspart and the need for new mealtime insulin analogues in adults with type 1 and type 2 diabetes: a Canadian perspective. Can J Diabetes. 2019;43(7):515–23.CrossRefPubMed
3.
4.
Heise T. Getting closer to physiologic insulin secretion. Clin Ther. 2007;29 Suppl D:S161–5.
5.
6.
Heinemann L, Heise T, Wahl LC, Trautmann ME, Ampudia J, Starke AA, et al. Prandial glycaemia after a carbohydrate-rich meal in type I diabetic patients: using the rapid acting insulin analogue [Lys(B28), Pro(B29)] human insulin. Diabet Med. 1996;13(7):625–9.CrossRef
7.
Humalog [package insert]. Indianapolis, IN: Eli Lilly and Company; 2017.
8.
Remodulin [package insert for US]. Research Triangle Park, NC: United Therapeutics; 2019.
9.
Pratt E, Leohr J, Heilmann C, Johnson J, Landschulz W. Treprostinil causes local vasodilation, is well tolerated, and results in faster absorption of insulin lispro. Diabetes. 2017;66(Suppl 1):A253.
10.
Paavola CD, Cox AL, Sperry AE, Hansen RJ, Li S, Bradley SA, et al. A stable, hexameric, ultra-rapid insulin formulation containing citrate. Diabetes. 2017;66 (Suppl 1):A254.
11.
Shiramoto M, Nasu R, Oura T, Imori M, Ohwaki K. Ultra-Rapid Lispro results in accelerated insulin lispro absorption and faster early insulin action in comparison to Humalog® in Japanese patients with type 1 diabetes. J Diabetes Investig. Epub 9 Dec 2019. https://​doi.​org/​10.​1111/​jdi.​13195.
12.
Blevins T, Zhang Q, Frias JP, Jinnouchi H, Chang AM. Randomized double-blind clinical trial comparing Ultra rapid lispro with Lispro in a basal-bolus regimen in patients with type 2 diabetes: PRONTO-T2D. Diabetes Care. 2020; (in press).
13.
Klaff LJ, Cao D, Dellva MA, Tobian J, Miura J, Dahl D, et al. Ultra rapid lispro (URLi) improves postprandial glucose (PPG) control vs. Humalog (Lispro) in T1D: PRONTO-T1D study. Diabetes. 2019;68 Suppl 1:144-OR.
14.
15.
16.
17.
Chow S, Liu J. Design and analysis of bioavailability and bioequivalence studies. 3rd ed. Boca Raton, FL: Taylor and Francis Group, LLC; 2009. pp. 88–90.
18.
Polonsky KS, Given BD, Van Cauter E. Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects. J Clin Invest. 1988;81(2):442–8.CrossRefPubMedPubMedCentral
19.
Defronzo RA. Glucose intolerance and aging: evidence for tissue insensitivity to insulin. Diabetes. 1979;28(12):1095–101.CrossRefPubMed
20.
21.
Minaker KL, Rowe JW, Tonino R, Pallotta JA. Influence of age on clearance of insulin in man. Diabetes. 1982;31(10):851–5.CrossRefPubMed
Metadata
Title
Pharmacokinetics and Glucodynamics of Ultra Rapid Lispro (URLi) versus Humalog® (Lispro) in Younger Adults and Elderly Patients with Type 1 Diabetes Mellitus: A Randomised Controlled Trial
Authors
Helle Linnebjerg
Qianyi Zhang
Elizabeth LaBell
Mary Anne Dellva
David E. Coutant
Ulrike Hövelmann
Leona Plum-Mörschel
Theresa Herbrand
Jennifer Leohr
Publication date
01-12-2020
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 12/2020
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-020-00903-0

Other articles of this Issue 12/2020

Clinical Pharmacokinetics 12/2020 Go to the issue

Current Opinion

The Interplay Between Liver First-Pass Effect and Lymphatic Absorption of Cannabidiol and Its Implications for Cannabidiol Oral Formulations

Acknowledgement to Referees

Acknowledgement to Referees

Original Research Article

Pharmacokinetic Assessment of Pre- and Post-Oxygenator Vancomycin Concentrations in Extracorporeal Membrane Oxygenation: A Prospective Observational Study

Original Research Article

Validation of a Drug Transporter Probe Cocktail Using the Prototypical Inhibitors Rifampin, Probenecid, Verapamil, and Cimetidine

Original Research Article

Pharmacokinetics and Glucodynamics of Ultra Rapid Lispro (URLi) versus Humalog® (Lispro) in Patients with Type 2 Diabetes Mellitus: A Phase I Randomised, Crossover Study

Original Research Article

Population Pharmacokinetic Analysis and Exploratory Exposure–Bleeding Rate Relationship of Emicizumab in Adult and Pediatric Persons with Hemophilia A