Association of TCF7L2 Gene Variants with Glycemic Control During Metformin Therapy in Type 2 Diabetes Mellitus

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Objective: The transcription factor 7-like 2 (TCF7L2) gene variants are among the strongest genetic risk factors for type 2 diabetes mellitus (T2DM). However, their influence on glycemic control during metformin therapy remains incompletely understood. This study aimed to investigate variants in the TCF7L2 gene and to evaluate their association with glycemic control in patients with T2DM receiving metformin therapy. Methods: Thirty-two patients diagnosed with T2DM were included in this study. The coding exons and exon–intron boundaries of the TCF7L2 gene were analyzed using next-generation sequencing. Glycemic control was assessed using HbA1c levels, and genotype–phenotype associations were evaluated. Results: Sequencing of the TCF7L2 gene identified multiple genetic variants, the majority of which were located within intronic and untranslated regions. Among these, 3 common intronic variants, rs2296782 (c.382-458A>G), rs56913138 (c.685+126G>T), and rs7903424 (c.788+252G>A), were selected for genotype–phenotype analyses. The rs7903424 variant was significantly associated with glycemic control. Mean HbA1c levels were 6.22 ± 0.44%, 7.36 ± 1.68%, and 6.30 ± 0.71% for the GG, GA, and AA genotypes, respectively. The rs7903424 GA genotype was significantly associated with poorer glycemic control compared with the GG genotype, as indicated by higher HbA1c levels (P = .020). Conclusion: The TCF7L2 rs7903424 polymorphism was associated with glycemic control in patients with T2DM receiving metformin therapy. The rs7903424 GA genotype was associated with significantly poorer glycemic control, as reflected by higher HbA1c levels, compared with the GG genotype. Cite this article as: Pekkoç-Uyanık K., Bayındır MY, Agay ER, Akdemir MF, Özyazgan S, Todurga-Seven ZG. Association of TCF7L2 gene variants with glycemic control during metformin therapy in type 2 diabetes mellitus. Cerrahpaşa Med J. 2026, 50, 0092, doi: 10.5152/cjm.2026.26092.

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