Genetic polymorphisms of GLUT1 (rs841853) and MATE1 (rs2289669) are associated with metformin response in type 2 diabetes mellitus

Introduction Metformin is first-line therapy for type 2 diabetes mellitus; however, over 30–40% of patients exhibit a suboptimal glycemic response. Metformin efficacy is governed by pharmacokinetic-pharmacodynamic processes. Cellular transport of metformin is influenced by Glucose transporter 1 (GLUT1) and renal elimination by multidrug and toxin extrusion protein 1 (MATE1). This study examined GLUT1 rs841853 and MATE1 rs2289669 polymorphisms on metformin response.Methods A total of 200 T2DM patients on metformin were recruited from Era’s Medical College and Hospital, Lucknow. Demographic, clinical, and biochemical data were collected. Genotyping of GLUT1 rs841853 and MATE1 rs2289669 was performed by PCR-RFLP. Statistical analysis was conducted using SPSS v27.Results GLUT1 GT and GG genotypes of rs841853 was higher in non‑responders than in responders (GT: 73.8% vs 66.0%) (OR = 2.494, q = 0.071) and (GG: 16.5% vs 12.4%) (OR = 2.975, q = 0.071). MATE1 A allele was higher in responders (28.3% vs 21.1%) with an OR of 0.628 (q = 0.219). Nominal significant associations in unadjusted analysis lost significance after multiple-testing correction. Gender-stratified analysis showed that female responders had a reduction in FBS, whereas non-responders had increased FBS, PPG and HbA1c levels in both males and females.Conclusion Findings emphasize a transporter-mediated pharmacogenetic approach and the potential value of combined GLUT1-MATE1 genotyping for individualized T2DM treatment.