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Pharmacogenetic aspects of vildagliptin treatment in patients with newly diagnosed type 2 diabetes mellitus

https://doi.org/10.21886/2219-8075-2019-10-3-83-90

Abstract

Objective: to study a role of the rs5219 polymorphism in KCNJ11 in the formation of the response variability to vildagliptin therapy in patients with newly diagnosed type 2 diabetes mellitus (T2DM).

Materials and methods: 48 patients with newly diagnosed T2DM were examined. For all patients vildagliptin in a dose of 50 mg/day was prescribed. If necessary, dose titration was carried out or other glucose-lowering therapy was prescribed for 6 months of observation. Dynamics of the main indicators of glycemic control and body mass index were studied, presence of the rs5219 polymorphism in KCNJ11 gene was also determined.

Results: all patients-carriers the T allele had achieved the target values of glycated hemoglobin (HbA1c) in 3 months of vildagliptin monotherapy, compared to patients with wild-type gene who achieved target values of HbA1c in only 44,4% of cases. Increasing the dose to 100 mg/day required 35% of patients with wild-type gene and 17.9% of patients with rs5219 polymorphism. The appointment of a combination of glucose-lowering therapy was necessary in 40% of patients with the wild-type gene and no one with polymorphism.

Conclusion: the presence of the polymorphic allele T rs5219 in KCNJ11 gene makes it possible to predict the high efficacy of vildagliptin monotherapy in patients with newly diagnosed T2DM.

About the Authors

P. B. Shorokhova
I.I. Mechnikov North-Western State Medcal University
Russian Federation

Polina B. Shorokhova - postgraduate student, V.G. Baranov Department of Endocrinology.

Saint Petersburg



V. L. Baranov
I.I. Mechnikov North-Western State Medcal University
Russian Federation

Vitaly L. Baranov - Doctor of Medical sciences, Professor of the V.G. Baranov Department of Endocrinology.

Saint Petersburg


N. V. Vorokhobina
I.I. Mechnikov North-Western State Medcal University
Russian Federation

Natalya V. Vorokhobina - Doctor of Medical sciences, Professor, Head of the V.G. Baranov Department of Endocrinology.

Saint Petersburg



I. Yu. Matezius
I.I. Mechnikov North-Western State Medcal University
Russian Federation

Irina Yu. Matezius - PhD, Assistant professor of the V.G. Baranov Department of Endocrinology.

Saint Petersburg



E. B. Bashnina
I.I. Mechnikov North-Western State Medcal University
Russian Federation

Elena B. Bashnina - Doctor of Medical sciences, Professor of the V.G. Baranov Department of Endocrinology.

Saint Petersburg



K. A. Jakovenko
I.I. Mechnikov North-Western State Medcal University
Russian Federation

Ksenia A. Jakovenko - 6th year student, medical faculty.

Saint Petersburg



References

1. DeFronzo RA. From the triumvirate to the ominous octet: A new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58(4):773–795. doi: 10.2337/db09-9028.

2. Schwartz SS, Epstein S, Corkey BE, Grant SFA, Gavin JR, Aguilar RB. The time is right for a new classification system for diabetes: rationale and implications of the β-cell–centric classification schema. Diabetes Care. 2016;39(8):179–186. http://doi.org/10.2337/dci16-0011.

3. Demidova TY., Kulenok SG., Gasanzade PA. Pathogenetic background of dipeptidyl peptidase-4 inhibitors application in the management of diabetes mellitus type 2. Consilium Medicum. 2017;19(4):23–28. (In Russ.). https://doi.org/10.26442/2075-1753_19.4.23-28.

4. Fonseca A, Schweizer D, Albrecht MA, Baron MA., Chang I., Dejager S. Addition of vildagliptin to insulin improves glycaemic control in type 2 diabetes. Diabetologia. 2007;50(6):1148–1155. https://doi.org/10.1007/s00125-007-0633-0

5. Dedov II, Shestakova MV, Ametov AS, Antsiferov MB, Galstyan GR, Mayorov AY et al. Initiation and intensification of antihyperglycemic therapy in type 2 diabetes mellitus: Update of Russian Association of Endocrinologists expert consensus document (2015) Diabetes mellitus. 2015;18(1):5-23. (in Russ.). doi: 10.14341/DM201515-23.

6. Aso Y, Ozeki N, Terasawa T, Naruse R, Hara K, Suetsugu M, et al. Serum level of soluble CD26/dipeptidyl peptidase-4 (DPP-4) predicts the response to sitagliptin, a DPP-4 inhibitor, in patients with type 2 diabetes controlled inadequately by metformin and/or sulfonylurea. Transl Res. 2012;159(1):25–31. doi: 10.1016/j.trsl.2011.09.005.

7. Semiz S., Dujic T., Causevic A. Pharmacogenetics and personalized treatment of type 2 diabetes. Biochem.Med. 2013; 23(2): 154–171. doi: 10.11613/BM.2013.020.

8. Jamaluddin JL, Huri HZ, Vethakkan SR, Mustafa N. Pancreatic gene variants potentially associated with dipeptidyl peptidase-4 inhibitor treatment response in Type 2 diabetes. Pharmacogenomics. 2014;15(2):235–249. http://doi.org/10.2217/pgs.13.234.

9. Dawed AY, Zhou K, Pearson ER. Pharmacogenetics in type 2 diabetes: influence on response to oral hypoglycemic agents. Pharmacogenomics and Personalized Medicine. 2016; 9:17–29. https://doi.org/10.2147/PGPM.S84854.

10. Haghvirdizadeh P, Mohamed Z, Abdullah NA, Haghvirdizadeh P, Haerian MS, Haerian BS. KCNJ11: Genetic Polymorphisms and Risk of Diabetes Mellitus. J Diabetes Res. 2015; 2015:908152. doi:10.1155/2015/908152.

11. Jamaluddin J.L., Huri H.Z., Vethakkan S.R. Clinical and genetic predictors of dipeptidyl peptidase-4 inhibitor treatment response in type 2 diabetes mellitus. Pharmacogenomics. 2016;17(8):867–881. doi: 10.2217/pgs-2016-0010.

12. Metody statisticheskoj obrabotki medicinskih dannyh: Metodicheskie rekomendacii dlja ordinatorov i aspirantov medicinskih uchebnyh zavedenij, nauchnyh rabotnikov. Ed. By Kochetov AG, Liang OV, Masenko VP, Zhirov IV, Nakonechnikov SN, Tereshchenko SN. Moscow: RKNPK; 2012. 42 p. (In Russ.)

13. Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck et al. Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred approach. Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia. 2015;58(3):429-442. doi:10.1007/s00125-014-3460-0

14. Ashcroft FM, Rorsman P. K(ATP) channels and islet hormone secretion: new insights and controversies. Nat Rev Endocrinol. 2013;9(11):660–669. doi:10.1038/nrendo.2013.166

15. Sastre J, Luque A, del Val F, Aragonés A, López J. Long-term efficacy of glibenclamide and sitagliptin therapy in adult patients with KCNJ11 permanent diabetes. Diabetes Care. 2014;37(3):e55-56. doi: 10.2337/dc13-2280


Review

For citations:


Shorokhova P.B., Baranov V.L., Vorokhobina N.V., Matezius I.Yu., Bashnina E.B., Jakovenko K.A. Pharmacogenetic aspects of vildagliptin treatment in patients with newly diagnosed type 2 diabetes mellitus. Medical Herald of the South of Russia. 2019;10(3):83-90. (In Russ.) https://doi.org/10.21886/2219-8075-2019-10-3-83-90

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