Abstract :
Metformin is often used as monotherapy or in combination when diet and exercise are not effective at lowering hyperglycemia. According to the American Diabetes Association, metformin is the preferred drug in newly diagnosed patients with type two diabetes mellitus in adults and children ten years and older. It is recommended as the first-line therapy for type 2 diabetes mellitus (T2DM) based on its efficacy, safety and low cost. In our research, we explored the impact of TCF7L2 gene single nucleotides polymorphisms (rs7903146) on metformin response in T2DM patients in Al-Diwaniyah governorate, Iraq. The current prospective cohort study included 61newly diagnosed patients with type 2 diabetes mellitus. The study was carried out at private clinic, Aldiwaniya governorate/ Iraq. The diagnosis of enrolled patients with T2DM done by an endocrinologist and they were on regular visits to the clinic for follow up. Levels of fasting serum glucose, HbA1c, insulin, HOMA IR, lipid profile, and anthropometric parameters were investigated before start metformin therapy, and 12 weeks after being treated. Genotyping of the TCF7L2 gene SNP was done by RFLP method. There was no significant change in mean HbA1c (p = 0.299); therefore, we chose the cutoff value of < 7% for HbA1c to split the group of patient into two groups, patients with HbA1c of < 7% were considered as glycemic controlled group (n = 22), and the group with HbA1c of ≥ 7 % were considered uncontrolled group (n = 39). We found significant association between TCF7L2 SNP (rs7903146) polymorphism and glycemic control according to an HbA1c cutoff of < 7 % (p = 0.032), in such a way that the heterozygous C/T genotype was more frequent in controlled group than in uncontrolled group, 45.5 % versus 15.4 %, respectively, while, both CC and TT homozygous genotypes were less frequent in controlled group than in uncontrolled group50.0 % versus 71.8 % and 4.5 % versus 12.8 %, respectively. The response to metformin therapy in T2DM patients in terms of glycemic control measured by HbA1c is affected significantly by TCF7L2 SNP (rs7903146 C>T) polymorphism in such a way that the heterozygous C/T genotype define better response.
