Genetic predictors of the pharmacological effects of dipeptidyl peptidase-4 inhibitors and sulfonylureas in patients with type 2 diabetes mellitus


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Abstract

The review presents current data on the pharmacogenetics of such oral antihyperglycemic drugs as dipeptidyl peptidase-4 (DPP-4) inhibitors and sulfonylureas (SU), whose mechanism of action is somehow related with the effect on the secretion of endogenous insulin. There is a significant variability in the glucose-lowering ability of DPP-4 inhibitors and SU, as well as in their side effects, pharmacokinetics (PK) and pharmacodynamics (PD). Majority of genetic studies focus on genetic polymorphisms involved in oral antihyperglycemic drugs (OADs) PK. Some recent studies, however, include genes encoding target molecules and transcription factors affecting the OAD PD. It is assumed that the therapeutic response to SU and DPP-4 inhibitors is widely associated with a number of single nucleotide polymorphisms in the TCF7L2, KCNJ11 and ABCC8 genes due to their crucial role in insulin secretion and glucose homeostasis. Significant progress has been achieved in determination of genetic markers associated with PD, therapeutic response and/or side effects of OADs. At the same time, despite the contradicting results of studies of various genetic factors that can cause a change in the glucose-lowering effect in response to taking antidiabetic drugs, the results of such reseach should undoubtedly be considered as the basis of the future pharmacogenetic recommendations for antihyperglycemic therapy in type 2 diabetes mellitus.

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About the authors

Polina B. Shorokhova

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

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

V. L Baranov

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

Department of Endocrinology n.a. Acad. V.G. Baranov St. Petersburg, Russia

N. V Vorokhobina

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

Department of Endocrinology n.a. Acad. V.G. Baranov St. Petersburg, Russia

O. S Shpilevaya

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

Department of Endocrinology n.a. Acad. V.G. Baranov St. Petersburg, Russia

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