Influence of SLC22A1 rs628031 and SLC47A1 rs2289669 genetic polymorphism on metformin response in South Indian type 2 diabetes patients – A cross-sectional study

Abstract Background: Metformin, an oral antidiabetic drug, is the first-line treatment for type 2 diabetes mellitus (T2DM). SLC22A1 and SLC47A1 play key roles in the transport and excretion of metformin, and genetic variations in these genes can significantly influence metformin disposition and therapeutic efficacy. The aim was to study the influence of SLC22A1 (rs628031) and SLC47A1 (rs2289669) genetic variants on the efficacy of metformin monotherapy in South Indian patients with T2DM. Materials and Methods: The study was a cross-sectional study, conducted for 18 months. Sixty-four T2DM patients have participated in the study. Patients’ demographic characteristics were collected. Glycated hemoglobin (HbA1c) values were determined using the nephelometry technique. The genetic polymorphisms were detected using a polymerase chain reaction-restriction fragment length polymorphism technique. Bonferroni test and one-way analysis of variance were used to evaluate the statistical significance of results. Results: This study revealed that T2DM patients on metformin monotherapy, fasting blood sugar, postprandial blood sugar, and HbA1c values were significantly lower among those with AG genotype (103.74 ± 28.15 mg/dl, 172.76 ± 50.4 mg/dl, and 6.99% ±1.50%) of SLC22A1 (rs628031) compared to AA (154.82 ± 52.58 mg/dl, 287.45 ± 109.21 mg/dl, and 9.92% ±1.73%) or GG genotype (136.75 ± 34.76 mg/dl, 237.00 ± 62.41 mg/dl, and 10.09% ±1.08%). However, no significant differences in glycemic control were observed among the AA, AG, and GG genotypes of the SLC47A1 (rs2289669) polymorphism. Conclusion: Metformin significantly lowers the blood glucose level in the AG genotype of SLC22A1 (rs628031) and has no significant association with SLC47A1 (rs2289669) in South Indian T2DM.