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

• Published in: Clinical and experimental medicine 2015-05, Vol.15 (2), p.159-165
• Main Authors: Mahrooz, Abdolkarim, Parsanasab, Hassan, Hashemi-Soteh, Mohammad Bagher, Kashi, Zahra, Bahar, Adele, Alizadeh, Ahad, Mozayeni, Maliheh
• Format: Article
• Language: English
• Subjects: Adult; Aged; Chemotherapy; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Drug therapy; Female; Genotype; Genotyping Techniques; Hematology; Humans; Internal Medicine; Male; Medical diagnosis; Medicine; Medicine & Public Health; Metformin - therapeutic use; Middle Aged; Oncology; Organic Cation Transporter 1 - genetics; Original Article; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Treatment Outcome
• ISSN: 1591-9528; 1591-8890; 1591-9528
• DOI: 10.1007/s10238-014-0283-8

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’ λ  = 0.905, p  = 0.01). Responders had significantly lower HbA1c and FBS levels compared with non-responders ( η 2  = 0.087, p  = 0.004 for HbA1c and η 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 ( η 2  = 0.067, p  = 0.01 for ALT and η 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.