title: The role of clinical response to metformin in patients newly diagnosed with type 2 diabetes: a monotherapy study.
abstract: 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.
authors.affiliation: Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Km 17 Khazarabad Road, Sari, Iran, kmahrooz@yahoo.com.
authors.forename: Abdolkarim
authors.initials: A
authors.lastname: Mahrooz
authors.forename: Hassan
authors.initials: H
authors.lastname: Parsanasab
authors.forename: Mohammad Bagher
authors.initials: MB
authors.lastname: Hashemi-Soteh
authors.forename: Zahra
authors.initials: Z
authors.lastname: Kashi
authors.forename: Adele
authors.initials: A
authors.lastname: Bahar
authors.forename: Ahad
authors.initials: A
authors.lastname: Alizadeh
authors.forename: Maliheh
authors.initials: M
authors.lastname: Mozayeni
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D027702:Organic Cation Transporter 1 / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D016896:Treatment Outcome
chemical_list: D027702:Organic Cation Transporter 1; D008687:Metformin
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