{"title":"Efsubaglutide Alfa对健康受试者二甲双胍和地高辛药动学的影响","authors":"Xiaojie Wu, Jinjie He, Junzhen Wu, Wei Liu, Yulong Xu, Yiming Li, Jing Zhang, Qinghua Wang","doi":"10.1007/s40262-025-01541-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Efsubaglutide alfa, as a novel glucagon-like peptide-1 receptor agonist, was developed for the treatment of type 2 diabetes mellitus. Its effect on the rate and extent of absorption of concomitant oral medications (digoxin and metformin) was evaluated in healthy participants.</p><p><strong>Methods: </strong>We conducted a single-center, open-label, fixed-sequence clinical trial involving 32 healthy participants who were assigned to either digoxin (N = 16) or metformin (N = 16) groups. The participants received oral doses of digoxin (0.25 mg, single dose) or metformin (1000 mg at first dose, 500 mg twice daily for 2 days) before and after subcutaneous injections of 3 mg efsubaglutide alfa at steady state. Pharmacokinetic parameters of digoxin and metformin before and after the administration of efsubaglutide alfa injections were measured, and safety assessments were conducted throughout the study.</p><p><strong>Results: </strong>Efsubaglutide alfa slightly delayed the time to reach peak plasma concentration (T<sub>max</sub>) of digoxin but had no substantial effect on its elimination. While the maximum concentration (C<sub>max</sub>) of digoxin decreased by approximately 24% (from 1.75 ± 0.673 to 1.37 ± 0.545 ng/mL), and AUC<sub>0-inf</sub> increased by about 15% (from 20.2 ± 3.53 to 23.2 ± 4.04 ng/h/mL). In the metformin group, efsubaglutide alfa did not noticeably affect T<sub>max</sub>, C<sub>max,ss</sub>, or the overall pharmacokinetics, as demonstrated by a consistent AUC<sub>0-tau</sub> (from 7557 ± 2155 to 8737 ± 2852 ng/h/mL). Adverse events with efsubaglutide alfa and co-administered medication were comparable to those reported during treatment with efsubaglutide alfa alone and were mostly gastrointestinal-related.</p><p><strong>Conclusions: </strong>No clinically significant pharmacokinetic change of digoxin and metformin was identified, and no new safety issues were observed with the co-administration of efsubaglutide alfa injection. These findings suggest that no dose adjustments are required for digoxin and metformin when co-administration with efsubaglutide alfa.</p><p><strong>Clinicaltrials: </strong></p><p><strong>Gov identifier: </strong>NCT05694221.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":""},"PeriodicalIF":4.6000,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effect of Efsubaglutide Alfa on the Pharmacokinetics of Metformin and Digoxin in Healthy Participants.\",\"authors\":\"Xiaojie Wu, Jinjie He, Junzhen Wu, Wei Liu, Yulong Xu, Yiming Li, Jing Zhang, Qinghua Wang\",\"doi\":\"10.1007/s40262-025-01541-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Efsubaglutide alfa, as a novel glucagon-like peptide-1 receptor agonist, was developed for the treatment of type 2 diabetes mellitus. Its effect on the rate and extent of absorption of concomitant oral medications (digoxin and metformin) was evaluated in healthy participants.</p><p><strong>Methods: </strong>We conducted a single-center, open-label, fixed-sequence clinical trial involving 32 healthy participants who were assigned to either digoxin (N = 16) or metformin (N = 16) groups. The participants received oral doses of digoxin (0.25 mg, single dose) or metformin (1000 mg at first dose, 500 mg twice daily for 2 days) before and after subcutaneous injections of 3 mg efsubaglutide alfa at steady state. Pharmacokinetic parameters of digoxin and metformin before and after the administration of efsubaglutide alfa injections were measured, and safety assessments were conducted throughout the study.</p><p><strong>Results: </strong>Efsubaglutide alfa slightly delayed the time to reach peak plasma concentration (T<sub>max</sub>) of digoxin but had no substantial effect on its elimination. While the maximum concentration (C<sub>max</sub>) of digoxin decreased by approximately 24% (from 1.75 ± 0.673 to 1.37 ± 0.545 ng/mL), and AUC<sub>0-inf</sub> increased by about 15% (from 20.2 ± 3.53 to 23.2 ± 4.04 ng/h/mL). In the metformin group, efsubaglutide alfa did not noticeably affect T<sub>max</sub>, C<sub>max,ss</sub>, or the overall pharmacokinetics, as demonstrated by a consistent AUC<sub>0-tau</sub> (from 7557 ± 2155 to 8737 ± 2852 ng/h/mL). Adverse events with efsubaglutide alfa and co-administered medication were comparable to those reported during treatment with efsubaglutide alfa alone and were mostly gastrointestinal-related.</p><p><strong>Conclusions: </strong>No clinically significant pharmacokinetic change of digoxin and metformin was identified, and no new safety issues were observed with the co-administration of efsubaglutide alfa injection. These findings suggest that no dose adjustments are required for digoxin and metformin when co-administration with efsubaglutide alfa.</p><p><strong>Clinicaltrials: </strong></p><p><strong>Gov identifier: </strong>NCT05694221.</p>\",\"PeriodicalId\":10405,\"journal\":{\"name\":\"Clinical Pharmacokinetics\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2025-06-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Pharmacokinetics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s40262-025-01541-0\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Pharmacokinetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40262-025-01541-0","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Effect of Efsubaglutide Alfa on the Pharmacokinetics of Metformin and Digoxin in Healthy Participants.
Background: Efsubaglutide alfa, as a novel glucagon-like peptide-1 receptor agonist, was developed for the treatment of type 2 diabetes mellitus. Its effect on the rate and extent of absorption of concomitant oral medications (digoxin and metformin) was evaluated in healthy participants.
Methods: We conducted a single-center, open-label, fixed-sequence clinical trial involving 32 healthy participants who were assigned to either digoxin (N = 16) or metformin (N = 16) groups. The participants received oral doses of digoxin (0.25 mg, single dose) or metformin (1000 mg at first dose, 500 mg twice daily for 2 days) before and after subcutaneous injections of 3 mg efsubaglutide alfa at steady state. Pharmacokinetic parameters of digoxin and metformin before and after the administration of efsubaglutide alfa injections were measured, and safety assessments were conducted throughout the study.
Results: Efsubaglutide alfa slightly delayed the time to reach peak plasma concentration (Tmax) of digoxin but had no substantial effect on its elimination. While the maximum concentration (Cmax) of digoxin decreased by approximately 24% (from 1.75 ± 0.673 to 1.37 ± 0.545 ng/mL), and AUC0-inf increased by about 15% (from 20.2 ± 3.53 to 23.2 ± 4.04 ng/h/mL). In the metformin group, efsubaglutide alfa did not noticeably affect Tmax, Cmax,ss, or the overall pharmacokinetics, as demonstrated by a consistent AUC0-tau (from 7557 ± 2155 to 8737 ± 2852 ng/h/mL). Adverse events with efsubaglutide alfa and co-administered medication were comparable to those reported during treatment with efsubaglutide alfa alone and were mostly gastrointestinal-related.
Conclusions: No clinically significant pharmacokinetic change of digoxin and metformin was identified, and no new safety issues were observed with the co-administration of efsubaglutide alfa injection. These findings suggest that no dose adjustments are required for digoxin and metformin when co-administration with efsubaglutide alfa.
期刊介绍：
Clinical Pharmacokinetics promotes the continuing development of clinical pharmacokinetics and pharmacodynamics for the improvement of drug therapy, and for furthering postgraduate education in clinical pharmacology and therapeutics.
Pharmacokinetics, the study of drug disposition in the body, is an integral part of drug development and rational use. Knowledge and application of pharmacokinetic principles leads to accelerated drug development, cost effective drug use and a reduced frequency of adverse effects and drug interactions.
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