Association of Single Nucleotide Polymorphism in OCT1 and OCT3 Genes with the Efficacy of Metformin Response in North Indian Type 2 Diabetes Mellitus Patients

Introduction: Variability in the effectiveness of metformin treatment among individuals with type 2 diabetes mellitus (T2DM) has been linked to various genetic factors. Understanding the genetic mechanisms underlying the action of metformin can greatly aid the personalized management of T2DM. Our investigation aimed to explore the impact of genetic variations in the organic cation transporters (OCT1 and OCT3) genes on the efficacy of metformin therapy in T2DM individuals from North India. Methods: This observational cross-sectional study assessed the influence of OCT1 (rs628031) and OCT3 (rs2292334) polymorphisms on metformin response in T2DM patients. Metformin response was determined based on HbA1c levels, dividing patients (n = 177) into two categories: responders (HbA1C<7%; n = 127) and non-responders (HbA1C≥7%; n = 50). Responders were further classified as T2DM patients receiving either monotherapy (n = 55) or combination therapy (n = 72). Genotyping was conducted using the PCR-RFLP method. Results: No significant association was observed between OCT1 (rs628031) polymorphism and metformin response in T2DM patients. However, a notable association was found between OCT3 (rs2292334) polymorphism and metformin response. Carriers of the AA genotype exhibited enhanced efficacy of metformin in both monotherapy (OR (CI)= 0.29(0.11-0.72), p=0.007) and combination therapy (OR (CI)= 0.41(0.16-1.0), p=0.047). Additionally, the A allele was more prevalent in responders (OR (CI)= 0.48(0.28-0.84), p=0.010), while the G allele was associated with reduced efficacy of metformin in T2DM patients (OR (CI)= 2.07(1.19-3.61), p=0.010). Conclusion: Genotyping of OCT3 (rs2292334) may serve as a valuable tool in predicting the response to metformin in T2DM patients.