Implication of critical pharmacokinetic gene variants on therapeutic response to metformin in Type 2 diabetes

Metformin, an oral hypoglycemic drug is the first line of treatment for Type 2 diabetes individuals. We studied the effect of critical gene single nucleotide polymorphisms on the glucose lowering effect of metformin. We performed a prospective study on 221 newly diagnosed, treatment-naive Type 2 diabetes subjects. Individuals were started with metformin monotherapy and followed up for 12 weeks. Our association analysis revealed that rs316019 and rs12943590 were significantly associated with metformin drug response across co-dominant and dominant models, respectively. rs316019 GG and rs12943590 GA combined genotypes showed maximum average change in HbA1c level. The present study proposes a role of rs316019 and rs12943590 in the pharmacokinetic action of metformin.