Pharmacokinetic Properties of a Once-Weekly Fixed-Ratio Combination of Insulin Icodec and Semaglutide Compared with Separate Administration of Each Component in Individuals with Type 2 Diabetes Mellitus
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| Název: | Pharmacokinetic Properties of a Once-Weekly Fixed-Ratio Combination of Insulin Icodec and Semaglutide Compared with Separate Administration of Each Component in Individuals with Type 2 Diabetes Mellitus |
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| Autoři: | Westergaard, Lisbet, Alifrangis, Lene, Buckley, Stephen T., Coester, Hans Veit, Klitgaard, Thomas, Kristensen, Niels R., Nishimura, Erica, Nørgreen, Lea, Rocha, Thaís M. P., Steensgaard, Dorte B., Vegge, Andreas, Plum-Mörschel, Leona |
| Zdroj: | Clin Drug Investig |
| Informace o vydavateli: | Springer Science and Business Media LLC, 2024. |
| Rok vydání: | 2024 |
| Témata: | Male, Adult, Cross-Over Studies, Adolescent, Injections, Subcutaneous, Glucagon-Like Peptides, Middle Aged, Drug Administration Schedule, Young Adult, Drug Combinations, Insulin/administration, Adolescent [MeSH], Double-Blind Method [MeSH], Female [MeSH], Adult [MeSH], Drug Combinations [MeSH], Humans [MeSH], Hypoglycemic Agents/pharmacokinetics [MeSH], Diabetes Mellitus, Type 2/drug therapy [MeSH], Drug Administration Schedule [MeSH], Middle Aged [MeSH], Diabetes Mellitus, Type 2/blood [MeSH], Insulin/pharmacokinetics [MeSH], Glucagon-Like Peptides/pharmacology [MeSH], Injections, Subcutaneous [MeSH], Male [MeSH], Cross-Over Studies [MeSH], Young Adult [MeSH], Glucagon-Like Peptides/administration, Original Research Article, Glucagon-Like Peptides/pharmacokinetics [MeSH], Hypoglycemic Agents/administration, Diabetes Mellitus, Type 2, Double-Blind Method, Humans, Hypoglycemic Agents, Insulin, Female |
| Popis: | IcoSema is being developed as a subcutaneous once-weekly fixed-ratio combination of the once-weekly basal insulin icodec and the once-weekly glucagon-like peptide-1 receptor agonist semaglutide. This study investigated the pharmacokinetics of icodec and semaglutide in IcoSema versus separate administration of each component in individuals with type 2 diabetes mellitus (T2DM).In a randomised, double-blind, three-period crossover study, 31 individuals with T2DM (18-64 years, body weight 80-120 kg, glycosylated haemoglobin 6.0-8.5%) received single subcutaneous injections of IcoSema (175 U icodec, 0.5 mg semaglutide), icodec (175 U) or semaglutide (0.5 mg) with 6-9 weeks' washout. Pharmacokinetic blood samples were drawn up to 840 h post-dose.Icodec pharmacokinetics were unaffected by combining icodec with semaglutide. The 90% confidence interval (CI) of IcoSema/icodec was within 0.80-1.25 for total exposure (area under the curve from zero to last quantifiable observation; AUC0-t: ratio [90% CI] 1.06 [1.01; 1.12]) and maximum concentration (Cmax): 1.12 [1.06; 1.18]. Semaglutide AUC0-t was also unaffected by combination with icodec (IcoSema/semaglutide 1.11 [1.05; 1.17]). However, semaglutide Cmax was higher for IcoSema versus semaglutide alone (IcoSema/semaglutide 1.99 [1.84; 2.15]) and occurred earlier for IcoSema (12 versus 84 h). Results of in vitro albumin binding studies and animal pharmacokinetic studies supported that the change in semaglutide absorption pharmacokinetics in IcoSema is owing to competition for albumin binding locally at the injection site with icodec outcompeting semaglutide. IcoSema, icodec and semaglutide were well-tolerated, although more gastrointestinal related adverse events occurred with IcoSema versus icodec or semaglutide alone.The combination of icodec and semaglutide in IcoSema leads to a higher and earlier maximum semaglutide concentration, which will guide the dose recommendations for IcoSema.ClinicalTrials.gov identifier: NCT03789578. |
| Druh dokumentu: | Article Other literature type |
| Jazyk: | English |
| ISSN: | 1179-1918 1173-2563 |
| DOI: | 10.1007/s40261-024-01405-8 |
| Přístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/39488821 https://repository.publisso.de/resource/frl:6521895 |
| Rights: | CC BY NC URL: http://creativecommons.org/licenses/by-nc/4.0/Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (http://creativecommons.org/licenses/by-nc/4.0/) . |
| Přístupové číslo: | edsair.doi.dedup.....ad1d1c9d3a678bc777e456352bca8056 |
| Databáze: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | IcoSema is being developed as a subcutaneous once-weekly fixed-ratio combination of the once-weekly basal insulin icodec and the once-weekly glucagon-like peptide-1 receptor agonist semaglutide. This study investigated the pharmacokinetics of icodec and semaglutide in IcoSema versus separate administration of each component in individuals with type 2 diabetes mellitus (T2DM).In a randomised, double-blind, three-period crossover study, 31 individuals with T2DM (18-64 years, body weight 80-120 kg, glycosylated haemoglobin 6.0-8.5%) received single subcutaneous injections of IcoSema (175 U icodec, 0.5 mg semaglutide), icodec (175 U) or semaglutide (0.5 mg) with 6-9 weeks' washout. Pharmacokinetic blood samples were drawn up to 840 h post-dose.Icodec pharmacokinetics were unaffected by combining icodec with semaglutide. The 90% confidence interval (CI) of IcoSema/icodec was within 0.80-1.25 for total exposure (area under the curve from zero to last quantifiable observation; AUC0-t: ratio [90% CI] 1.06 [1.01; 1.12]) and maximum concentration (Cmax): 1.12 [1.06; 1.18]. Semaglutide AUC0-t was also unaffected by combination with icodec (IcoSema/semaglutide 1.11 [1.05; 1.17]). However, semaglutide Cmax was higher for IcoSema versus semaglutide alone (IcoSema/semaglutide 1.99 [1.84; 2.15]) and occurred earlier for IcoSema (12 versus 84 h). Results of in vitro albumin binding studies and animal pharmacokinetic studies supported that the change in semaglutide absorption pharmacokinetics in IcoSema is owing to competition for albumin binding locally at the injection site with icodec outcompeting semaglutide. IcoSema, icodec and semaglutide were well-tolerated, although more gastrointestinal related adverse events occurred with IcoSema versus icodec or semaglutide alone.The combination of icodec and semaglutide in IcoSema leads to a higher and earlier maximum semaglutide concentration, which will guide the dose recommendations for IcoSema.ClinicalTrials.gov identifier: NCT03789578. |
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| ISSN: | 11791918 11732563 |
| DOI: | 10.1007/s40261-024-01405-8 |