ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Clinical Diabetes
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1536402
METFORMIN EFFICACY AND TOLERANCE ACCORDING TO GENETIC POLYMORPHISMS OF ORGANIC CATION TRANSPORTER 1 IN TUNISIAN PATIENTS WITH TYPE 2 DIABETES
Provisionally accepted
Fatma Chaker1,2*
Amani Kallel1,3Nadia Khessairi1,2Meriiem Yazidi1,2
Ibtissem Oueslati1,2Hiba Allah Chatti2
Moncef Feki1,2
Melika Chihaoui1,2- 1Hôpital La Rabta, Tunis, Tunisia
- 2Faculty of Medicine, Tunis El Manar University, Tunis, Tunis, Tunisia
- 3Tunis El Manar University, Tunis, Tunisia
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Purpose: Metformine efficacy and tolerance, at equivalent dose, is variable in type 2 diabetes. Inter-individual variability in the response to metformin with about 35% of patients failing to achieve initial glycemic control may be explained by genetic polymorphisms that interfere with the pharmacokinetics and pharmacodynamics of metformin. Variability in pharmacogenomic risk allele frequencies associated with metformin effects explains in some cases interethnic differences in drug responses. The aims of this study were to assess the effect of three polymorphisms of SLC22A1 encoding for the OCT1; M420del, R61c, and G401S on metformin response and tolerance in a cohort of Tunisian type 2 diabetes patients Methods: This was a prospective study, including 73 newly-diagnosed type 2 diabetic patients. Patients underwent a clinical and biological assessment before and three months after treatment by metformin. Patients were genotyped for the M420del, R61c, and G401S polymorphism of SLC22A1 by Polymerase Chain Reaction (PCR) followed by Restriction Fragment Length Polymorhism (RFLP). We defined metformin efficacy by HbA1c reduction ≥ 1% and metformin induced gastrointestinal adverse events using a questionnaire Results: Thirty-nine patients (53%) were responders to metformin. M420del, R61C and G401S variants did not affect the response to metformin (p: 0.8, p: 0.77, and p: 0.49 respectively). Twenty-seven patients (37%) developed gastrointestinal adverse events after metformin initiation. The G401S polymorphism and the haplotype (NoDel) CA were significantly associated with gastrointestinal adverse events.In tunisian type 2 diabetes, M420del and R61C seem not to be associated with the efficacy or the digestive intolerance to metformin. The G401S polymorphism could be implicated in the occurrence of metformine-induced gastrointestinal adverse events.
Keywords: adverse effects, glycemic control, Metformin, Organic Cation Transporter 1, Pharmacogenetics, SLC22A1, type 2 diabetes
Received: 28 Nov 2024; Accepted: 09 Jun 2025.
Copyright: © 2025 Chaker, Kallel, Khessairi, Yazidi, Oueslati, Chatti, Feki and Chihaoui. 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: Fatma Chaker, Hôpital La Rabta, Tunis, Tunisia
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