Differentiated approach to metformin therapy in newly diagnosed type 2 diabetes mellitus from the perspective of pharmacogenetics


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Abstract

Background. Metformin remains the first-line drug for newly diagnosed type 2 diabetes mellitus (T2DM). It has been shown that common genetic variants affect the glycemic response to metformin, which explains up to 34% of the variability in the decrease in glycated hemoglobin (HbA1c) during treatment with this drug. Further studies are required to clarify the effect of the KCNJ11 rs5219 and TCF7L2 rs7903146 variants on the individual therapeutic effect of metformin and to determine the significance of genotyping results for these polymorphisms in the development of a differentiated approach to therapy in patients with newly diagnosed T2DM. Objective. Evaluation of the role of KCNJ11 rs5219 and TCF7L2 rs7903146 polymorphisms in the formation of an individual response to metformin therapy in patients with newly diagnosed T2DM. Methods. The prospective cohort study included 77 patients with newly diagnosed T2DM who received initial metformin therapy. The dynamics of the main indicators of glycemic control and body mass index (BMI) was assessed over 6 months of treatment. All patients were genotyped for the KCNJ11 rs5219 (C>T) and TCF7L2 rs7903146 (C>T) polymorphisms using the real-time polymerase chain reaction technique. Results. After 6 months of metformin treatment, the KCNJ11 rs5219 variant was associated with significantly greater reductions in BMI, fasting blood glucose, and HbA1c in newly diagnosed T2DM (P<0.05). No association was found between the carriage of the TCF7L2 rs7903146 polymorphism and the individual response to metformin in the studied cohort of patients. Conclusion. Our results show that patients with newly diagnosed T2DM with the KCNJ11 rs5219 polymorphism are more susceptible to metformin therapy than carriers of the wild genotype. No data have been obtained on the effect of the TCF7L2 rs7903146polymorphism on the therapeutic effect of metformin in patients with newly diagnosed T2DM.

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About the authors

Polina B. Shorokhova

North-Western State Medical University n.a. I.I. Mechnikov

Email: poliamina@gmail.com
Endocrinologist, Postgraduate Student, Department of Endocrinology n.a. Academician V.G. Baranov Saint Petersburg, Russia

V. L Baranov

North-Western State Medical University n.a. I.I. Mechnikov

Department of Endocrinology n.a. Academician V.G. Baranov Saint Petersburg, Russia

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