Influence of GLUT2 rs8192675, MATE1 rs2289669, and OCT2 rs316019 Genetic Polymorphism on Metformin Efficacy and Glycemic Control in Type 2 Diabetes Mellitus Patients

Abstract Metformin, being the gold standard drug of choice in type 2 diabetes mellitus (T2DM) shows differential therapeutic response in patients due to gene polymorphism. The objective of this study was to investigate the influence of GLUT2 rs8192675, MATE1 rs2289669, and OCT2 rs316019 being hotspot single nucleotide polymorphisms (SNPs) on metformin efficacy and glycemic control in T2DM. In current research work, 417 subjects were enrolled, of which 200 were healthy control, and 217 newly diagnosed T2DM patients, involving 60 metformin non-responding and 157 metformin responding individuals. The patients were subjected to three months of metformin monotherapy and their initial and final HbA1c, BMI, fasting glucose, and lipid profiles were determined. Genotyping was performed through real-time PCR with melt curve analysis followed by agarose gel electrophoresis and Sanger sequencing. GLUT2 rs8192675 CC genotype (OR 0.24, CI 95% 0.06–0.84, p = 0.02) and MATE1 rs2289669 A allele (OR 0.14, CI 95% 0.05–0.33, p < 0.0001) were significantly associated with metformin response and glucose-lowering effect. No significant association ( p > 0.05) was observed for OCT2 rs316019. GLUT2 rs8192675 CC genotype and MATE1 rs2289669 A allele are significantly associated with low glucose and HbA1c levels, positively altering metformin efficacy in newly diagnosed T2DM responsive individuals.