Fangfang Wang, Zijian Luan, Raluca Maltesen, Asbjørn T Reenberg, Lisbet Westergaard, Dongyang Liu
{"title":"中国2型糖尿病患者每周一次胰岛素与西马鲁肽联合治疗与其单独成分的药代动力学特征","authors":"Fangfang Wang, Zijian Luan, Raluca Maltesen, Asbjørn T Reenberg, Lisbet Westergaard, Dongyang Liu","doi":"10.1007/s13300-025-01803-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>IcoSema is under development as a once-weekly injectable combination therapy of icodec (basal insulin) and semaglutide (glucagon-like peptide 1 receptor agonist). This study assessed the pharmacokinetic characteristics of icodec and semaglutide following IcoSema administration vs. administration of icodec and semaglutide alone in Chinese individuals with type 2 diabetes (T2D).</p><p><strong>Methods: </strong>In a randomized, double-blind, three-period crossover study, 20 Chinese individuals with T2D (18-64 years, body mass index 18.5-34.9 kg/m<sup>2</sup>, glycated hemoglobin ≤ 9.0%) were given single subcutaneous administrations of IcoSema, icodec, or semaglutide separated by 6-9 weeks. Blood was drawn for pharmacokinetic measurement until 840 h post dose.</p><p><strong>Results: </strong>Combining icodec with semaglutide had no impact on icodec pharmacokinetics. The ratio and 90% confidence interval of IcoSema/icodec was 1.04 [0.99;1.08] for area under the curve from zero to last quantifiable observation (AUC<sub>0-t</sub>) and 1.02 [0.96;1.09] for maximum concentration (C<sub>max</sub>), i.e., within the bioequivalence acceptance interval of 0.80-1.25. Likewise, combining semaglutide with icodec had no impact on semaglutide AUC<sub>0-t</sub> (IcoSema/semaglutide 0.99 [0.94;1.05]). However, semaglutide C<sub>max</sub> was higher for IcoSema vs. semaglutide alone (1.42 [1.31;1.53]) and occurred earlier for IcoSema (12 vs. 66 h). All three treatments were safe with no differences in frequency, severity or outcome of adverse events, or relationship to study product.</p><p><strong>Conclusion: </strong>In Chinese individuals with T2D, icodec pharmacokinetics and semaglutide total exposure are unaffected when combining icodec and semaglutide in IcoSema. However, maximum semaglutide concentration is higher and occurs earlier with IcoSema. This information may help to ensure suitable dose recommendations for IcoSema.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier, NCT05435677.</p>","PeriodicalId":11192,"journal":{"name":"Diabetes Therapy","volume":" ","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pharmacokinetic Characteristics of a Once-Weekly Combination Therapy of Insulin Icodec and Semaglutide Versus Its Separate Components in Chinese Individuals with Type 2 Diabetes.\",\"authors\":\"Fangfang Wang, Zijian Luan, Raluca Maltesen, Asbjørn T Reenberg, Lisbet Westergaard, Dongyang Liu\",\"doi\":\"10.1007/s13300-025-01803-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>IcoSema is under development as a once-weekly injectable combination therapy of icodec (basal insulin) and semaglutide (glucagon-like peptide 1 receptor agonist). This study assessed the pharmacokinetic characteristics of icodec and semaglutide following IcoSema administration vs. administration of icodec and semaglutide alone in Chinese individuals with type 2 diabetes (T2D).</p><p><strong>Methods: </strong>In a randomized, double-blind, three-period crossover study, 20 Chinese individuals with T2D (18-64 years, body mass index 18.5-34.9 kg/m<sup>2</sup>, glycated hemoglobin ≤ 9.0%) were given single subcutaneous administrations of IcoSema, icodec, or semaglutide separated by 6-9 weeks. Blood was drawn for pharmacokinetic measurement until 840 h post dose.</p><p><strong>Results: </strong>Combining icodec with semaglutide had no impact on icodec pharmacokinetics. The ratio and 90% confidence interval of IcoSema/icodec was 1.04 [0.99;1.08] for area under the curve from zero to last quantifiable observation (AUC<sub>0-t</sub>) and 1.02 [0.96;1.09] for maximum concentration (C<sub>max</sub>), i.e., within the bioequivalence acceptance interval of 0.80-1.25. Likewise, combining semaglutide with icodec had no impact on semaglutide AUC<sub>0-t</sub> (IcoSema/semaglutide 0.99 [0.94;1.05]). However, semaglutide C<sub>max</sub> was higher for IcoSema vs. semaglutide alone (1.42 [1.31;1.53]) and occurred earlier for IcoSema (12 vs. 66 h). All three treatments were safe with no differences in frequency, severity or outcome of adverse events, or relationship to study product.</p><p><strong>Conclusion: </strong>In Chinese individuals with T2D, icodec pharmacokinetics and semaglutide total exposure are unaffected when combining icodec and semaglutide in IcoSema. However, maximum semaglutide concentration is higher and occurs earlier with IcoSema. This information may help to ensure suitable dose recommendations for IcoSema.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier, NCT05435677.</p>\",\"PeriodicalId\":11192,\"journal\":{\"name\":\"Diabetes Therapy\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2025-10-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetes Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s13300-025-01803-x\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13300-025-01803-x","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
Pharmacokinetic Characteristics of a Once-Weekly Combination Therapy of Insulin Icodec and Semaglutide Versus Its Separate Components in Chinese Individuals with Type 2 Diabetes.
Introduction: IcoSema is under development as a once-weekly injectable combination therapy of icodec (basal insulin) and semaglutide (glucagon-like peptide 1 receptor agonist). This study assessed the pharmacokinetic characteristics of icodec and semaglutide following IcoSema administration vs. administration of icodec and semaglutide alone in Chinese individuals with type 2 diabetes (T2D).
Methods: In a randomized, double-blind, three-period crossover study, 20 Chinese individuals with T2D (18-64 years, body mass index 18.5-34.9 kg/m2, glycated hemoglobin ≤ 9.0%) were given single subcutaneous administrations of IcoSema, icodec, or semaglutide separated by 6-9 weeks. Blood was drawn for pharmacokinetic measurement until 840 h post dose.
Results: Combining icodec with semaglutide had no impact on icodec pharmacokinetics. The ratio and 90% confidence interval of IcoSema/icodec was 1.04 [0.99;1.08] for area under the curve from zero to last quantifiable observation (AUC0-t) and 1.02 [0.96;1.09] for maximum concentration (Cmax), i.e., within the bioequivalence acceptance interval of 0.80-1.25. Likewise, combining semaglutide with icodec had no impact on semaglutide AUC0-t (IcoSema/semaglutide 0.99 [0.94;1.05]). However, semaglutide Cmax was higher for IcoSema vs. semaglutide alone (1.42 [1.31;1.53]) and occurred earlier for IcoSema (12 vs. 66 h). All three treatments were safe with no differences in frequency, severity or outcome of adverse events, or relationship to study product.
Conclusion: In Chinese individuals with T2D, icodec pharmacokinetics and semaglutide total exposure are unaffected when combining icodec and semaglutide in IcoSema. However, maximum semaglutide concentration is higher and occurs earlier with IcoSema. This information may help to ensure suitable dose recommendations for IcoSema.
期刊介绍：
Diabetes Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all areas of diabetes. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged.
The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Diabetes Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.
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