ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Drug Metabolism and Transport
This article is part of the Research TopicIntegrated PK/PD and Drug Metabolism Approaches in Drug Development and EvaluationView all 12 articles
Population Pharmacokinetics of Efpeglenatide in individuals with obesity and with type 2 diabetes
Provisionally accepted
- 1Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, College of Medicine, University of Ulsan, SONGPA-GU, Republic of Korea
- 2University of Ulsan College of Medicine, Department of Medical Science and Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, Songpa-gu, Republic of Korea
- 3Hanmi Pharmaceuticals Co Ltd, Songpa-gu, Republic of Korea
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Background: Efpeglenatide (HM11260C) is a long-acting GLP-1 receptor agonist under development for obesity. A population pharmacokinetic (PK) analysis was conducted to characterize its PK properties and evaluate covariate effects to support clinical dosing strategies. Methods: Pooled PK data from six clinical studies in participants with type 2 diabetes or obesity were analyzed using nonlinear mixed-effects modeling (NONMEM). Covariate effects, model diagnostics, and simulations were used to assess exposure and dosing strategies. Results: A two-compartment model with dual absorption pathways adequately described the data. Body weight and disease status influenced absorption and clearance; however, predicted exposure differences across weight percentiles and demographic subgroups were modest and within conventional bioequivalence limits. Simulations suggested approximately dose-proportional increases across the evaluated dose range with once-weekly administration and supported the feasibility of stepwise dose-escalation. Conclusion: Efpeglenatide PK was well characterized across type 2 diabetes and obesity populations. Although some covariates affected PK parameters, their impact on exposure was not clinically meaningful. These results support a uniform dosing strategy without routine dose adjustment and provide quantitative evidence for stepwise dose escalation in ongoing clinical development for obesity.
Keywords: Efpeglenatide, HM11260C, GLP-1 receptor agonist, PopulationPharmacokinetics, Obesity, Modeling and Simulation, Dose optimization, NONMEM
Received: 29 Sep 2025; Accepted: 20 Nov 2025.
Copyright: © 2025 Choi, Seo, Park, Kim, Kim and Lim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Hyeong-Seok Lim, mdhslim@gmail.com
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