ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacogenetics and Pharmacogenomics
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1686415
A Digital Twin of Glimepiride for Personalized and Stratified Diabetes Treatment
Provisionally accepted
- Humboldt University of Berlin, Berlin, Germany
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Optimizing glimepiride therapy for type 2 diabetes (T2DM) is challenged by pronounced inter-individual variability in pharmacokinetics. We developed a whole-body physiologically based pharmacokinetic (PBPK) model as a digital twin of glimepiride, enabling systematic evaluation of how patient-specific factors influence drug disposition. Using curated data from 20 clinical studies, the digital twin mechanistically simulates glimepiride's absorption, distribution, metabolism, and excretion (ADME). It accounts for key determinants of variability including renal and hepatic function, CYP2C9 genotype, and bodyweight. The model accurately reproduced observed pharmacokinetics and quantified these factors' impact on drug exposure. Increased glimepiride exposure was predicted in individuals with hepatic dysfunction or specific CYP2C9 variants, highlighting substantial genetic and physiological effects. This digital twin provides mechanistic insights into pharmacokinetic variability and serves as an in silico platform for exploring individualized dosing and patient stratification strategies, laying the foundation for clinical decision support tools to improve T2DM management.
Keywords: Digital Twin, diabetes, Glimepiride, PBPK, physiologically based pharmacokinetic model, pharmacokinetics, Personalizedmedicine
Received: 15 Aug 2025; Accepted: 16 Sep 2025.
Copyright: © 2025 Elias and König. 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: Matthias König, konigmatt@googlemail.com
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