The role of clinical response to metformin in patients newly diagnosed with type 2 diabetes: a monotherapy study

A major predicament in certain users of metformin, which is one of the most commonly used antihyperglycemic agents for type 2 diabetes (T2DM) treatment, is the lack of appropriate response to the drug. We evaluated the role of metformin response and OCT1 (organic cation transporter1) Met420del polymorphism in a monotherapy study (metformin therapy for 12 weeks) on patients newly diagnosed with T2DM. Based on the response to metformin, patients (n = 108) were divided into two groups: responders (n = 49) and non-responders (n = 59). HbA1c levels were determined by affinity technique. The OCT1-Met420del polymorphism was genotyped by PCR-based restriction fragment length polymorphism. There was a significant association between the variable response with HbA1c and fasting blood sugar (FBS) (Wilks' lambda = 0.905, p = 0.01). Responders had significantly lower HbA1c and FBS levels compared with non-responders (eta(2) = 0.087, p = 0.004 for HbA1c and eta(2) = 0.055, p = 0.022 for FBS). The interaction treatment-response increased the effect sizes from 32 to 58 % for HbA1c. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values were significantly lower in the responder group than in the non-responders (eta(2) = 0.067, p = 0.01 for ALT and eta(2) = 0.052, p = 0.025 for AST). This observational study showed that the variant OCT1-Met420del may be more effective on plasma glucose than HbA1c. The variable response could account for a significant proportion of the variance in HbA1c levels observed following treatment with metformin. Metformin shows a significantly greater effect on ALT and AST in responders than in non-responders.