Skip to main content
Top
Published in:

Open Access 09-05-2024 | Insulins | Original Research Article

The Effect of Various Degrees of Renal or Hepatic Impairment on the Pharmacokinetic Properties of Once-Weekly Insulin Icodec

Authors: Hanne Haahr, Blanka Cieslarová, Janne R. Hingst, Shan Jiang, Niels R. Kristensen, Viera Kupčová, Lea Nørgreen, Frank-Dietrich H. Wagner, Stanislav Ignatenko

Published in: Clinical Pharmacokinetics | Issue 6/2024

Login to get access

Abstract

Background and Objective

Icodec is a once-weekly insulin being developed to provide basal insulin coverage in diabetes mellitus. This study evaluated the effects of renal or hepatic impairment on icodec pharmacokinetics.

Methods

Two open-label, parallel-group, single-dose (1.5 U/kg subcutaneously) trials were conducted. In a renal impairment trial, 58 individuals were allocated to normal renal function (measured glomerular filtration rate ≥ 90 mL/min), mild (60 to < 90 mL/min), moderate (30 to < 60 mL/min) or severe (< 30 mL/min) renal impairment or end-stage renal disease. In a hepatic impairment trial, 25 individuals were allocated to normal hepatic function or mild (Child-Pugh Classification grade A), moderate (grade B) or severe (grade C) hepatic impairment. Blood was sampled frequently for a pharmacokinetic analysis until 35 days post-dose.

Results

The shape of the icodec pharmacokinetic profile was not affected by renal or hepatic impairment. Total icodec exposure was greater for mild (estimated ratio [95% confidence interval]: 1.12 [1.01; 1.24]), moderate (1.24 [1.12; 1.37]) and severe (1.28 [1.16; 1.42]) renal impairment, and for end-stage renal disease (1.14 [1.03; 1.28]), compared with normal renal function. It was also greater for mild (1.13 [1.00; 1.28]) and moderate (1.15 [1.02; 1.29]) hepatic impairment versus normal hepatic function. There was no statistically significant difference between severe hepatic impairment and normal hepatic function. Serum albumin levels (range 2.7–5.1 g/dL) did not statistically significantly influence icodec exposure.

Conclusions

The clinical relevance of the slightly higher icodec exposure with renal or hepatic impairment is limited as icodec should be dosed according to individual need. No specific icodec dose adjustment is required in renal or hepatic impairment.

Clinical Trial Registration

ClinicalTrials.gov identifiers: NCT03723785 and NCT04597697.
Appendix
Available only for authorised users
Literature
15.
go back to reference Philis-Tsimikas A, Asong M, Franek E, et al. Switching to once-weekly insulin icodec versus once-daily insulin degludec in individuals with basal insulin-treated type 2 diabetes (ONWARDS 2): a phase 3a, randomised, open label, multicentre, treat-to-target trial. Lancet Diabetes Endocrinol. 2023;11:414–25. https://doi.org/10.1016/S2213-8587(23)00093-1.CrossRefPubMed Philis-Tsimikas A, Asong M, Franek E, et al. Switching to once-weekly insulin icodec versus once-daily insulin degludec in individuals with basal insulin-treated type 2 diabetes (ONWARDS 2): a phase 3a, randomised, open label, multicentre, treat-to-target trial. Lancet Diabetes Endocrinol. 2023;11:414–25. https://​doi.​org/​10.​1016/​S2213-8587(23)00093-1.CrossRefPubMed
18.
go back to reference Mathieu C, Ásbjörnsdóttir B, Bajaj HS, et al. Switching to once-weekly insulin icodec versus once-daily insulin glargine U100 in individuals with basal-bolus insulin-treated type 2 diabetes (ONWARDS 4): a phase 3a, randomised, open-label, multicentre, treat-to-target, non-inferiority trial. Lancet. 2023;401:1929–40. https://doi.org/10.1016/S0140-6736(23)00520-2.CrossRefPubMed Mathieu C, Ásbjörnsdóttir B, Bajaj HS, et al. Switching to once-weekly insulin icodec versus once-daily insulin glargine U100 in individuals with basal-bolus insulin-treated type 2 diabetes (ONWARDS 4): a phase 3a, randomised, open-label, multicentre, treat-to-target, non-inferiority trial. Lancet. 2023;401:1929–40. https://​doi.​org/​10.​1016/​S0140-6736(23)00520-2.CrossRefPubMed
Metadata
Title
The Effect of Various Degrees of Renal or Hepatic Impairment on the Pharmacokinetic Properties of Once-Weekly Insulin Icodec
Authors
Hanne Haahr
Blanka Cieslarová
Janne R. Hingst
Shan Jiang
Niels R. Kristensen
Viera Kupčová
Lea Nørgreen
Frank-Dietrich H. Wagner
Stanislav Ignatenko
Publication date
09-05-2024
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 6/2024
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-024-01375-2

Other articles of this Issue 6/2024

Clinical Pharmacokinetics 6/2024 Go to the issue