{"title":"Pharmacokinetic and Pharmacodynamic Properties of Once-Weekly Insulin Efsitora Alfa in Japanese Patients with Type 2 Diabetes.","authors":"Risa Nasu, Tomonori Oura, Kenji Ohwaki, Makoto Imori, Kenichi Furihata","doi":"10.1007/s13300-025-01695-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>This analysis aimed to assess the safety and tolerability of insulin efsitora alfa (efsitora, basal insulin Fc, LY3209590) and characterize the pharmacokinetic and pharmacodynamic profiles of efsitora in Japanese patients with type 2 diabetes.</p><p><strong>Methods: </strong>The single-dose escalation study assessed once-weekly efsitora administration in three patient cohorts: 5 mg for cohort 1; 10 mg for cohort 2 or placebo under double-blind conditions; and 20 mg for cohort 3 under open-label conditions. In the 6-week, multiple-dose study, patients started or continued using insulin degludec during the lead-in period, followed by randomization to efsitora (individualized fixed weekly dose) or insulin degludec (individualized fixed daily dose). Pharmacokinetics, pharmacodynamics, and safety were examined.</p><p><strong>Results: </strong>The mean age was 58.3 and 58.4 years, and mean body mass index was 25.6 and 26.8 kg/m<sup>2</sup> in the single-dose escalation (n = 31) and multiple-dose studies (n = 28), respectively. The pharmacokinetic profile showed a prolonged half-life of 15 to 16 days, with a low peak-to-trough ratio of 1.13 after the last dose with little fluctuation. All doses of efsitora (5, 10, and 20 mg) decreased mean fasting glucose levels from baseline to day 15 (single-dose study), with no notable changes observed after switching from insulin degludec (multiple-dose study). All treatment-emergent adverse events were mild and unrelated to the study drug. No severe hypoglycemic events were reported.</p><p><strong>Conclusions: </strong>Efsitora was well tolerated, and the pharmacokinetic and pharmacodynamic profiles were consistent with findings in prior global studies, supporting the participation of Japanese patients in phase 3 studies.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT03603704; NCT04276428.</p>","PeriodicalId":11192,"journal":{"name":"Diabetes Therapy","volume":" ","pages":"513-526"},"PeriodicalIF":3.8000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11868009/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13300-025-01695-x","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/10 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
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Abstract
Introduction: This analysis aimed to assess the safety and tolerability of insulin efsitora alfa (efsitora, basal insulin Fc, LY3209590) and characterize the pharmacokinetic and pharmacodynamic profiles of efsitora in Japanese patients with type 2 diabetes.
Methods: The single-dose escalation study assessed once-weekly efsitora administration in three patient cohorts: 5 mg for cohort 1; 10 mg for cohort 2 or placebo under double-blind conditions; and 20 mg for cohort 3 under open-label conditions. In the 6-week, multiple-dose study, patients started or continued using insulin degludec during the lead-in period, followed by randomization to efsitora (individualized fixed weekly dose) or insulin degludec (individualized fixed daily dose). Pharmacokinetics, pharmacodynamics, and safety were examined.
Results: The mean age was 58.3 and 58.4 years, and mean body mass index was 25.6 and 26.8 kg/m2 in the single-dose escalation (n = 31) and multiple-dose studies (n = 28), respectively. The pharmacokinetic profile showed a prolonged half-life of 15 to 16 days, with a low peak-to-trough ratio of 1.13 after the last dose with little fluctuation. All doses of efsitora (5, 10, and 20 mg) decreased mean fasting glucose levels from baseline to day 15 (single-dose study), with no notable changes observed after switching from insulin degludec (multiple-dose study). All treatment-emergent adverse events were mild and unrelated to the study drug. No severe hypoglycemic events were reported.
Conclusions: Efsitora was well tolerated, and the pharmacokinetic and pharmacodynamic profiles were consistent with findings in prior global studies, supporting the participation of Japanese patients in phase 3 studies.
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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