Influence of OCT2 gene variants on metformin efficacy in type 2 diabetes: insights into pharmacogenomics and drug interactions
Abstract Metformin, a widely prescribed treatment for type 2 diabetes mellitus (T2DM), demonstrates significant inter-individual variability in its therapeutic response. This variability is potentially driven by genetic differences in drug transporters. Among these transporters, the organic cation t...
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BMC
2025-08-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06720-y |
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| author | Ma’mon M. Hatmal Omar Abuyaman Mohammad A. I. Al-Hatamleh Heba Tayyem Amin N. Olaimat Ali Mussa Iman Aolymat Aymen Abuawad Mohanad Odeh Rana Qawaqzeh |
| author_facet | Ma’mon M. Hatmal Omar Abuyaman Mohammad A. I. Al-Hatamleh Heba Tayyem Amin N. Olaimat Ali Mussa Iman Aolymat Aymen Abuawad Mohanad Odeh Rana Qawaqzeh |
| author_sort | Ma’mon M. Hatmal |
| collection | DOAJ |
| description | Abstract Metformin, a widely prescribed treatment for type 2 diabetes mellitus (T2DM), demonstrates significant inter-individual variability in its therapeutic response. This variability is potentially driven by genetic differences in drug transporters. Among these transporters, the organic cation transporter 2 (OCT2) plays a critical role in the pharmacokinetics of metformin by mediating its uptake into renal epithelial cells for excretion. This review explores the potential impact of genetic variations in OCT2 gene (SLC22A2) on the pharmacokinetics and pharmacodynamics of metformin. These genetic variations can alter metformin accumulation in the kidneys, impacting its overall clearance and therapeutic effectiveness. Furthermore, the interactions of metformin with other drugs, especially in T2DM patients, can compromise its pharmacokinetics. Thus, it is important to consider the influence of genetic variability and potential drug interactions when prescribing metformin. Incorporating genetic testing into clinical decision-making could help optimize dosing strategies and improve treatment outcomes, particularly when managing patients with complex comorbid conditions. |
| format | Article |
| id | doaj-art-2c2ad25285e74cd1b51bc4651cc2e219 |
| institution | DOAJ |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-2c2ad25285e74cd1b51bc4651cc2e2192025-08-20T03:05:57ZengBMCJournal of Translational Medicine1479-58762025-08-0123112310.1186/s12967-025-06720-yInfluence of OCT2 gene variants on metformin efficacy in type 2 diabetes: insights into pharmacogenomics and drug interactionsMa’mon M. Hatmal0Omar Abuyaman1Mohammad A. I. Al-Hatamleh2Heba Tayyem3Amin N. Olaimat4Ali Mussa5Iman Aolymat6Aymen Abuawad7Mohanad Odeh8Rana Qawaqzeh9Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, The Hashemite UniversityDepartment of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, The Hashemite UniversityUPMC Hillman Cancer Center, Division of Malignant Hematology and Medical Oncology, Department of Medicine, University of Pittsburgh School of MedicineDepartment of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, The Hashemite UniversityDepartment of Clinical Nutrition and Dietetics, Faculty of Applied Medical Sciences, The Hashemite UniversityDepartment of Hematology, School of Medical Sciences, Universiti Sains MalaysiaDepartment of Anatomy, Physiology and Biochemistry, Faculty of Medicine, The Hashemite UniversityGenoLabsDepartment of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmaceutical Sciences, The Hashemite UniversityFaculty of Medicine, The Hashemite UniversityAbstract Metformin, a widely prescribed treatment for type 2 diabetes mellitus (T2DM), demonstrates significant inter-individual variability in its therapeutic response. This variability is potentially driven by genetic differences in drug transporters. Among these transporters, the organic cation transporter 2 (OCT2) plays a critical role in the pharmacokinetics of metformin by mediating its uptake into renal epithelial cells for excretion. This review explores the potential impact of genetic variations in OCT2 gene (SLC22A2) on the pharmacokinetics and pharmacodynamics of metformin. These genetic variations can alter metformin accumulation in the kidneys, impacting its overall clearance and therapeutic effectiveness. Furthermore, the interactions of metformin with other drugs, especially in T2DM patients, can compromise its pharmacokinetics. Thus, it is important to consider the influence of genetic variability and potential drug interactions when prescribing metformin. Incorporating genetic testing into clinical decision-making could help optimize dosing strategies and improve treatment outcomes, particularly when managing patients with complex comorbid conditions.https://doi.org/10.1186/s12967-025-06720-yT2DMInsulinOrganic cation transportersSNPSLC22A2808G > T |
| spellingShingle | Ma’mon M. Hatmal Omar Abuyaman Mohammad A. I. Al-Hatamleh Heba Tayyem Amin N. Olaimat Ali Mussa Iman Aolymat Aymen Abuawad Mohanad Odeh Rana Qawaqzeh Influence of OCT2 gene variants on metformin efficacy in type 2 diabetes: insights into pharmacogenomics and drug interactions Journal of Translational Medicine T2DM Insulin Organic cation transporters SNP SLC22A2 808G > T |
| title | Influence of OCT2 gene variants on metformin efficacy in type 2 diabetes: insights into pharmacogenomics and drug interactions |
| title_full | Influence of OCT2 gene variants on metformin efficacy in type 2 diabetes: insights into pharmacogenomics and drug interactions |
| title_fullStr | Influence of OCT2 gene variants on metformin efficacy in type 2 diabetes: insights into pharmacogenomics and drug interactions |
| title_full_unstemmed | Influence of OCT2 gene variants on metformin efficacy in type 2 diabetes: insights into pharmacogenomics and drug interactions |
| title_short | Influence of OCT2 gene variants on metformin efficacy in type 2 diabetes: insights into pharmacogenomics and drug interactions |
| title_sort | influence of oct2 gene variants on metformin efficacy in type 2 diabetes insights into pharmacogenomics and drug interactions |
| topic | T2DM Insulin Organic cation transporters SNP SLC22A2 808G > T |
| url | https://doi.org/10.1186/s12967-025-06720-y |
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