Influence of OCT2 gene variants on metformin efficacy in type 2 diabetes: insights into pharmacogenomics and drug interactions.

Mohanad Odeh, Iman Aolymat, Ali Mussa, Omar Abuyaman, Ma'mon M Hatmal, Amin N Olaimat, Mohammad A I Al-Hatamleh, Heba Tayyem, Aymen Abuawad, Rana Qawaqzeh

Journal: Journal of translational medicine 2025;23(1):884

PMID: 40775340

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.

© 2025. The Author(s).

Address: Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, The Hashemite University, P.O. Box 330127, Zarqa, 13133, Jordan. [email protected].; Department of Pathology, School of Medicine, Stanford University, 300 Pasteur Drive, Stanford, CA, 94305, USA. [email protected].; Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, The Hashemite University, P.O. Box 330127, Zarqa, 13133, Jordan.; UPMC Hillman Cancer Center, Division of Malignant Hematology and Medical Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Department of Clinical Nutrition and Dietetics, Faculty of Applied Medical Sciences, The Hashemite University, Zarqa, Jordan.; Department of Hematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.; Department of Biology, Faculty of Education, Omdurman Islamic University, Omdurman, Sudan.; Department of Anatomy, Physiology and Biochemistry, Faculty of Medicine, The Hashemite University, Zarqa, Jordan.; GenoLabs, Amman, Jordan.; Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmaceutical Sciences, The Hashemite University, Zarqa, Jordan.; Faculty of Medicine, The Hashemite University, Zarqa, Jordan.
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