of genetic research, a multiplex approach to determining the pharmacotherapy tactics has become possible, taking into account the individual characteristics of the patient. Nevertheless, the modern tactics of pharmacotherapy "to failure" has been adopted, which over time leads to the intensification of therapy. A personalized approach to the pharmacotherapy of type 2 diabetes mellitus by determining the genotype of endothelial synthase of nitric oxide will predict the effectiveness of metformin monotherapy in the debut of the disease and reduce the risk of decompensation and complications with long-term type 2 diabetes mellitus. The aim of the study was to monitor the effectiveness of metformin pharmacotherapy for long-term type 2 DM, depending on the patient's genotype. Materials and methods: A single-center, randomized, prospective study of 200 patients referred for planned hospitalization. The single nucleotide polymorphism of the gene eNOS3, the level of glycated hemoglobin. Homeostatic model 2 (HOMA 2) was applied to evaluate insulin resistance in patients. In consistency with the results, patients were divided into three groups: with the ??, TC and TT genotype. Results and discussion: Patients of the CC genotype group achieved and kept glycated hemoglobin below the target level in 80% of cases, when metformin was used at a dose of 1700 mg per day. No one of the patients, who representatives of the TC and TT genotypes reached the target values of glycated hemoglobin. Thus, the use of metformin as monotherapy to compensate for carbohydrate metabolism is not enough for TC and TT genotypes, and combination hypoglycemic pharmacotherapy, including insulin therapy, is required. Conclusion: Identification of the presence of a particular eNOS3 gene allele provides the possibility of earlier prescribing appropriate drugs in an individual dose to reduce insulin resistance and likely limit the progression of diabetes mellitus, as well as increase the degree of compensation for carbohydrate metabolism. # Keywords 1![10. Patent for invention RU ?2626670 S2, 2017 Sorokina Yu.A., Zanozina O.V., Lovcova L.V., Seropyan M.Yu. Method for predicting the effectiveness of treatment of patients with type 2 diabetes. 11. Dedov I.I, Shestakova M.V., Majorov A.Yu. Algorithms for specialized medical care for patients with diabetes. 9 th ed. M.: UP PRINT; 2019. 212 p [In Russian] 12. The Oxford Centre for Diabetes, Endocrinology and Metabolism. ver 2.2.3, https://www.dtu.ox.ac.uk/ homacalculator/ 13. Ametov A.S., Prudnikova M.A. Sustained release metformin is a new standard in the treatment of type 2 diabetes. Endokrinologiya: novosti, mneniya, obuchenie. 2015. 1:19-26 [In Russian] 14. Zanozina O.V., Sorokina Yu.A., Lovcova L.V., Urakov A.L. Gliptins in incretin-directed pharmacotherapy of diabetes mellitus: opportunities and personalization. Remedium Privolzh'e (Nizhnij Novgorod). 2018. 112 p. ??????????? ??????? ??????????????. ???????????? ?? A. T. Hattersle, K. A. Patel [2].](image-2.png "??????? 1 :") ?????????????? ?????????? ?????????????????????? ? ??????????????????????????? ??? ????????? ??????? ?Ð?" 2 ??????????-????????: ? ????????? ??????????? ???????????? ???????????? ???? ????????? ?????????????? ?????? ? ??????????? ??????? ?????????????? ? ?????? ?????????????? ???????????? ? ?? ?????????, ?.?. ????????? ??????????????? ??????????????? ??????????????, ??????????????????????????????????????????????????????????????????????????????????????? ? ???????? ?????: ???????? ?????? 2 ????,?????????????? ???????, ?????????, ??????????????? eNOS3, ??????????????????????.Abstract-Introduction: With the development of the availability 16 Year 2020 Global Journal of Medical Research Volume XX Issue VIII Version I ( D D D D ) Year 2020 18 Volume XX Issue VIII Version I D D D D ) ( Medical Research Global Journal of: type 2 diabetes mellitus, monotherapy, methformin, eNOS3 gene polymorphism, insulin resistance. I. ???????? ???????????, ??? ???????? ?????? (?Ð?") ???????? ?????? ?????????????? ????????. ???????? ?????? ????????????? ????????? ???????, ????? 415 ???. ??????? ?? ???? ???? ???????? ?Ð?" 2 ????, ? ?? ??????????????? ????????? ? 2040 ?. ??? ????? ????????? 642 ???. ??? ????, ?? ?????? ?????? 320,5 ???. ????????? ? ?Ð?" 2 ???? ????????? ? ?????? ??????????????? ????????? ?? 20 ?? 64 ??? [1]. ?????????????? ???????? ???????? ????? ? ??????? ?Ð?". ??????????????? ????????????? ???????? ??????????? ? ??????? ???????????????? ?Ð?" ? ?? ??? ??????????? ????? ????????. ????????? ?????????? ?????????????? ?Ð?" ????????: ???????????????? ??????, ???? ????????????? ???????????, ???????????? ????????????? ??? ???????????? ????????????. ? ?????????? ??????????? ??????? ??????????? ?Ð?" ??? ??????? ??????????? ??????? ???????????? ???????????? ???? ????????? ?????????????? ?????? ? ??????????? ??????? ?????????????? ? ?????? ?????????????? ???????????? ???????? (??????? 1) [2]. ? ??????? ?? ?????????? ???? ??????? (MODY, ???????????? ?????? ? ????????? ??????), ?Ð?" 2 ???? ??????????????? ?????????? ???????? ? ??????????? ?????, ??????? ?????????? ?? ?????? ???????? ? ??????? ??????? ???????????, ?? ? ????? ?? ??????????????, ???????? «??????? ????????» [3]. ?? ?????? ?????? ??????? ?????????? ???????????? ????????????? ? ???????????? ??????????????? ?????????? ? ??????????? ?? ??????? ?????, ????????? ? ????????? ?Ð?" 2 ???? (PPARG, DIPOR2, ADAMTS9, IRS1, GCKR, KLF14, ADIPOQ), ????????? ? ??????? ????????????? ?????????? (SUR1, GLPR-1), ? ????? ???????? ?? ??????????????? ????????? (MATE ? ???). ?????? ??????? ???????????? ??????? ?????, ??????????? ? ??????????????? ??????????????? ??????? ?????????????? ???????. ????????, ???????? ???? ????????????????? ? ????, ??????????? ?? ???????? ??????????? ???????? [4]. ?? ???? ?????????????? ????? ?????????????? ?Ð?" 2 ???? ?????????? ?????????????? ???????????? ????????? ???????? ??????????? ?????????? ?? ?????????????????? ???????? ? ????????? ?Ð?" ? ??? ?????????? ??????? ? ??????????????? ?????????, ??? ????????? ?????????????? ?????????????, ? ??????????, ????????? ????????????? ????????? ???? ? ????????? ?????????????? ??????? ??????? ????? ??? ?? 1,0 %, ?? ??????? ????? ???????? ? ??????????? (???????????? ?????????? ???????? ????????? ??? ?????????? ????????????????). ??? ???? ??????????? ????????? ???? ???????? ?bA1c ? 0,5 % ?? 6 ??????? ?????????? [11]. ?????? ? ???????? ??????? ?????? ????????? ????????? ?????????????? ??????? ?????????? ????, ??? ?????????? ??????? ??????????? ?????????????? ??????????? ??? ???????????? ??????? ?????????? ???????????. ? ????? ? ????, ????? ???????????? ???? ?????????? ????????????? ?????????????? ??????????? ????????? ???????? ?Ð?" 2 ???? ? ??????????? ?? ???????? ????????. II. ????????? ? ?????? Ð?"????? ????????????: ????????????? ????????????? ????????????????? ????????????. ??????????? ?????????? ?? ????????? ????????????? ?????????????? ? ????????? ??????????? ? ??????????? ?? ???????? ???????? ??? ??????????? ? ??????? ???????? ?????????????? ?????????). ???????????????? ??????????? ???? (???) eNOS3 (rs 2070744) ?????????? ??????? ???????????? ?????? ??????? ? ???????? ??????? ??? ????????????? ??????????? ??????? (??? «?????», ??????). Ð?"???????????? ?????????? ?????????? ?? ?????????? ???????????? Bio-Rad ?? ???????????? ???????? (???????). ??????? ?-???????, ????????????? ??? ??????? ??????????? HOMA 2-IR, HOMA 2-B ? HOMA 2-IS ???????????????? ??????, ????????? ? ??????? ??????????????? ???????????????? ????-?????? «Mercodia C-peptide ELISA specific». ??? ?? ???? ?? ?????????????? ????????? ?? ? ?? ?? ?????? ??????? ???????? ?????????????? 2. Hattersle ?.?., Patel ?.?. Precision diabetes: learning from monogenic diabetes. Diabetologia. ???????????. ??? ???? HbA1c ? ????????? ??????? 2017. 60:769-777 DOI 10.1007/s00125-017-4226-2. ?????????? ?? (0,14) ???????, ??? 60,00 [55,00;64,00] Ð?"??????????? ?Ð?" 2 ????, ??? 9,5 [ 6,0;10,25 ] ??????? HbA 1 c, % Ð?"?????????? HbA 1 c, 6,90 [5,9;7,8] *p=0,029 ??????????????? ?????????????? ????????? ??????? ??????????? ???????? ????????? Ð?"??-4 ????? ?? ??? ????????? ????????????? ??????????, ?????????????? ?????????????? ??? ???? ?????? ??????????????????????. ????????? ??????? ??? ???????? ???????? ? ????????? ???????? ??????? ????????. ?????????? ?????? ??????????????? ? ???, ??? ??? ?? ? ?? ????????? ?????????? ?????????? ? ???????? ??????????? ??? ??????????? ??????????? ?????? ????????????. ???? ???? ????????????? ????????????? ?????????????? ?????????????? ?Ð?" ????? ?????????? 3. ???????? ?.?., ??????? ?.?., ?????? ?.?., ???????? ?.?. Ð?"??????????? ??????????? ? ????????? ? ??????? ?????????? ???????? ???????? 2-?? ????. ??????????? ?????????? ? 2019. 11 (2):57-62. DOI: ????????. 10.17691/stm2019.11.2.08 ??????????????? ??????????????? ??????????????, ? ??? ????? ???????????????. ? ????????? ?? ???????? ????????? ??????????? ?????????-???????? ????? ? ???????? ??????? ???????????????????? ? ?????????????????????? (??), ???????? ????-?????? ?? ???????????? ??????????? [13], ?? ???? ???? ?? ???????? ???????????????? ?????????????? ??, ??? ??????? ????????? ? ?????????? HOMA2, ? ?????????? ????????? ????????? ??????? ????-??????. ? ?? ????? ??? ? ????????? ? ??????, ????????, ???????????? ?????? ?????????? ?? ???????????????????? ?? ??????????? ? ?????? ???? ??-?? ???????????? 4. Rotroff D.M. et al. Genetic Variants in CPA6 and PRPF31 Are Associated With Variation in Response to Metformin in Individuals With Type 2 Diabetes Diabetes. 2018;67:1428-1440 5. Ð?"???? ?.?., ??????????? ?.?., ???????? Ð?".?., ?????????? ?.?., ?????????? ?.?., ?????? ?.?., ??????? Ð?".?., ???????? ?.?. ??????? 2: ?????????? ?????????????????????? ? ????????? ? ?????????? ?????????? ??? ?????????? ?Ð?" 2 ???? Atlas. 8th ed. Brussels: IDF, 2017. ?????????? HbA1c ????????? ? ??????? ????????? ??? ???????????? ?? ????????? ????????? ?????????? ?????????? ???????????. ??????????????-???????????? ?????????????? ???? ????????, ??? ????? ??????????? ?????????? ???????? ?????????, ??? ? ???????????, ??? ? ? ?????????? ? ??????? ???????????. ??? ???? ? ????? ????????? ??????? ???????????? ????????????? ???????? (?b? 1 ?>8%), ? ??????????? ??????? ???? ???????? ??????? ?? ???? ?? ????? ??????????? ?????????? ?Ð?" [5]. ??????? ????? ?????? ?????????? ?????? ??????????? ???????? ???????? ?????????? ?????????????????? ?????????. ?? ??????? ?????????? ?Ð?" ?????????? 57% ?????? ??????????? ??????, ????? ??? ?? ???? ??????????????? ??????? -????? 10% [6]. ????? ???????????? ?????? ? ?????????????? ????? ??????? ??? ????????? ??????? «?? ???????». ?? ????, ? ???????????? ? ??????????????, ? ??????????? ?? ????????? ?????? ?????????? ??????????? ??????????? ?????? ??????????? ?? ??? ???? ?????????????? ? ??????????? ????????? ?? ???? 1 ???? ? ????? ? ? ????????? ??????? ?? ?????????????? ?? ???????, ??? ????? 6 ???????. ? ???? ??? ????? ??????? ????????? ?????????????? ?Ð?" 2 ????, ??????? ????? ?? ??????????? ??????????, ??? ???????? ?????????? ???????????? ???????, ????????? ????????????? ? ?????? ????????? ??? ?Ð?" ?????????? ?????????? [7]. ? ????? ? ????, ?????? ???????? ??????????? ??????????????? ????????????? ?????????????? ?Ð?" 2 ???? ??? ?? ????? ??????????? ?? ???????. ? ???? ????? ??? ?????????? ?????? ??????????????? ????????????? ??????? ??????? ?Ð?" 2 ???? ??????????? ? ??????????? ???? 1700 ?? ? ????? ??? ?????????? ??? ? ???????? ???????????, ??????? ??????? ?? ??????????? ???????? ?????????????? ??????? ?????? ????? (eNOS3) ? ????????? ? ?????? ??????????? ? ?????????????????? ????????? ???????? ? ????? ???????? ?????????????. ????? ???? ??? ????????? ???, ??? ????????? ???????? ????????? ?????? ????? (NO) [8] ? ???????? NO-????????? ?????????? ??????? [9]. ???????????, ??? ????? ??? ?????? ?????????? ?????????? ? ???? 1700 ??/????? ? ???? ????????? ? ????????? ?? ??????????? ??????????? ???????? ???????????????? ?? 1% ? ?????????? ??? ??????? ???????? [10]. ? ????????? ? ?????????? ?? ? ?? ?? ??? ?????? ?????????????? ??????????? ???????? ???????? ?????? ???????? ? ?????????????? ??????????? ?????????????, ? ??? ??????????????? ?? 6 ??????? ????? ?? ??????? ????????? ?????????????????? ???????? ???????? HbA1c ?? 0,5-1% [11]. ??????? ????????, ??? ??? ??????????? ????????? ???????? ???????? ??? ?????????????????? ??????????? ??????? ???????? ?????????????? ??????????? ?????????? ????? 7%. ???? ???????? ?????????????? ????????? ?????????? ?????? ??????????? ????????????????? ?????? ???????. ???????? ????? ???????????? ???????? ????????? ? ???????????????? ???? eNOS3, ???????? ?? ????????? ?????????? ????????????? ? ?????? ????? ????? ??????????. ????????? ?????????? ??????? U ???????? ?????-?????. ???????? ????? ?????????? ???????? ??????????? ? ??????? ???????? ??????????. ?????????? ???????????? ? ????: ??????? [25% ????????;75% ????????]. ?????? ??????????? ???????????????? ?????? 2 (????2) ????????? ? ??????? ??????????????????? ??????????, ?????????????? ??????????? ?????????????, ?????? 2.2.3 [12]. III. ?????????? ? ?????????? Ð?"????? ????????? ? ?????????? ??? eNOS3 ??, ?? ? ?? ???? ??????????? ?? ????, ????????, ???????????? ?Ð?" 2 ????, ??????? ????????????? ??????????? ? ????????????? ??????????, ????????????? ??????????????. ??? ??????? ???????????? ?Ð?" 2 ???? 10 ??? ? ????????????? ????????? ??????? ?????????? ?????????????? ??????????? ???????? 7,5%. ??? ???? ????? ????????? ? ????????? ?? ???????? ? ?????????? ??????? ?????????????? ??????????? ???? ???? ???????? 80% ??????? ??? ?????????? ?????????? ? ???? 1700 ?? ? ????? ? ??????? ????????? ???????????? ??????????? ? ??????????????? ???????????? ??? ???????. ?????????? ????????? ???????? ? ???????? ??????????????, ??????????? ? ???????????????, ??????? ?? ????????? ? ??????? ????? ??????? ??????? ????????? ??????????? ? ?????? ?????????? (??????? 1). Ð?"?????? (??????? ?????????????) ?? (0,45) ?? (0,41) 59,50 [55,00;66,00] 65,50 [58,00;69,00] 10,2 [ 10,0;13,25 ] 10,0 [5,0;14,5 ] 7,5 8,61 [8,0;9,5] 8,5 [7,6;10,20] ????????? ?????????? ?????? ?????????? ??????????????-2 ??????? ??????????? ? ????????? ???????? ????????? Ð?"??-4 ????????? ?????????? ?????? ?????????? ????????? ???????? 1. International Diabetes Federation. IDF Diabetes ????????? Ð?"??-4 ?????????? ??????? ??????????? ? [14]. ??????????????-2 ?????????? ????????????? ??????? ??, ?????????? ??? ????????????? ????????? ??????? «?? ???????». ??????????? ???? ???????????????? ?????? ?????? 2 (????2), ????????? ?????????????? ????????? ??????? ????-?????? (%B) ? ???????????????? ? ???????? (%S), ? ????????? ?? ?????????? ??????????? ?????????, ? ????? ??????? ?????????????? ?????????????????????? (??). ? ????????? ? ?? ?????????, ???????? ?? ??????? ?????????? ???????????????? ????-??????, ?????? ?????????????? ?? (HOMA2-IR) ??????? ? ??????? ? ?????????????? ?????? ?????????. ??? ????? ????????????????? ? ???, ???, ???????? ?? ??????????? ??????????? ??????????? ??????, ????????? ????-?????? ? ????????? ? ?? ????????? ????????, ?? ????????????? (??????? 2). ? ??????????? ??????????? (Me [25p;75p]) ?????????? Ð?"?????? (??????? ?????????????) ?? (0,14) ?? (0,45) ?? (0,41) HOMA 2-IR (??????? ?????????????? ??) 3,5 [1,86;3,64] 3,79 [1,13;4,14] 4,47 [2,34;5,25] HOMA ????????????????????????? ??????? ??????????? ???????? ????????? ? ???????? ???????? 2 ????: ?????????? ??????????? ??????????????? ??????????????? ??????????????????? ???????????? ???????-?Ð?" 2. ???????? ??????. 2016. 19(6): doi: 10.14341/DM8146 6. Ð?"???? ?.?., ??????????? ?.?., ???????? Ð?".?., ?????? ?.?., ?????????? ?.?., ??????? ?.?., ??????????? ?.?., ?????? ?.Ð?"., ????? ?.?. ?????? ????????? ??????? ????????? ??????? 2 ???? ? ?????????? ?????????: ?????????? ??????????? ??????????????? ??????????????? ?????????????????????????? ???????????? ???????-?Ð?"2. ???????? ??????. 2017. 20(6):403-419. doi: 10.14341/DM9278 7. ????????? ?????????????????? ??????????? 2-B (?????????????? ????????? ??????? ????-??????, % ?? ???????????) 93,2 [67, 88;177,2] *?=0,0078 54,3 [35,7;65,5 ] 46,9 [29,7;74,85] HOMA 2-IS (???????????????? ? ????????, % ?? ??????????) 34,7333 [27,5;53,8] 26,4 [24,1;88,8] 31,45[19,05;42,65] ??????????. ? -??????? ?????????????? ??????????. IV. ??????????. ????? ???????, ?? ?????? ?????????????, ????????????? ?????????? ??????? ???????? ????????? ????????, ?? ? ?????????????? ?????????? ??????????????????????, ? ??? ????? ?????????? ???????????? ???? eNOS3. ????????? ??????? ???? ??? ????? ?????? ??????? ???????????? ???? ????????????? ??????????? ?????? ??????? ???????? ????????. ??? ????????? ?.?. Ð?"?????, ?.?. ??????????, ?.?. ????????. 8-? ??????. ?.: ?? ?????; 2018. 8. ???????? ?.?., ?????????? ?.?., ????????? ?.?., ????? ?.?. ???? ?????????? ??? ?????? ?????? ????? ? ????????? ??????????? ?????? ? ????????? ? ???????? ???????? 2 ????. ???????? ??????. 2013. 16(3):41-45 9. Alvim R.O. et al. General aspects of muscle glucose uptake. Anais da Academia Brasileira de Ciências. 2015. 87(1): 351-368 (Annals of the Brazilian Academy of Sciences) [In Portugal] 10. ?????? ?? ??????????? RU ?2626670 ?2, 2017 ???????? ?.?., ???????? ?.?., ??????? ?. ?., ??????? ?. ?. ?????? ??????????????? ??????????? ????? ??????? ?????????? ??????????????? ?????????? ????????????? ??????? ??????? ???????? ?????????????????????? ???????? ?????? ?????? ?????????? ?Ð?" 2 ???? ? ???????????? ??????? ????????????????? ?????????, ? ????????????? ???????????? ?????????????? ?????????????? -? ?????????????? ???? ??? ???????? ???????? 2 ????. ?????????????????????? ? ?????????? ??????????? 11. ????????? ?????????????????? ??????????? ???????????????? ????????? ???????, ? ????? ?????????? ??????? ??????????? ??????????? ?????? ?????? ??????? ???????? ????????.17 Year 2020 Global Journal of Medical Research Volume XX Issue VIII Version I ( D D D D )??????????: HbA 1????????????? ??????????; ???????? ?????????????? ??????????; Ð?"?????????????????????.B © 2020 Global Journals Insulin Resistance and Pharmacotherapy Effectiveness in Patients with Long -Term Diabetes Mellitus Type 2 ??????? 1: ?????????????? ????? ? ??????? ?????????????? ??????????? ? ??????????? ?? ???????? ????????? ??? ?????????? ?Ð?" 2 ???? ? ??????????? ??????????? (Me [25p;75p]) B © 2020 Global Journals Insulin Resistance and Pharmacotherapy Effectiveness in Patients with Long -Term Diabetes Mellitus Type 2 © 2020 Global Journals Insulin Resistance and Pharmacotherapy Effectiveness in Patients with Long -Term Diabetes Mellitus Type 2 * International Diabetes Federation. IDF Diabetes Atlas 2017 8th ed. Brussels: IDF * Precision diabetes: learning from monogenic diabetes ??Hattersle ??Patel 10.1007/s00125-017-4226-2 Diabetologia 60 2017 * Genetic Polymorphism in Patients with Newly Diagnosed Type 2 Diabetes Mellitus. Sovremennye tekhnologii v medicine SorokinaYu .ALovtsova LVUrakov ALZanozina OV 10.17691/stm2019.11.2.08 2019 11 In Russian * Genetic Variants in CPA6 and PRPF31 Are Associated With Variation in Response to Metformin in Individuals With Type 2 Diabetes Diabetes DMRotroff 2018 67 * Assessing routine healthcare pattern for type 2 diabetes mellitus in Russia:the results of ?harmacoepidemiological study (FORSIGHT-DM2) IIDedov MFKalashnikova DYBelousov VVRafalskii VYKalashnikov ASKolbin DRYazykova LRIvanenko 10.14341/DM8146 Diabetes mellitus 19 6 2016 In Russian * Cost-of-Illness Analysis of Type 2 Diabetes Mellitus in the Russian Federation: Results from Russian multicenter, observational, pharmacoepidemiologic study of diabetes care for patients with type 2 diabetes mellitus (FORSIGHT-?2DM). Diabetes mellitus IIDedov MFKalashnikova DYBelousov ASKolbin VVRafalskiy AECheberda MAKantemirova VDZakiev VVFadeyev doi: 10.14341/ DM9278 2017 20 In Russian * Algorithms for specialized medical care for patients with diabetes IIDedov MVShestakova AMajorov Yu th ed. M.: UP PRINT; 2019. 212 p [In Russian * The role of metformin as a nitric oxide donor in the regulation of carbohydrate metabolism in patients with type 2 diabetes. Diabetes ISKuznecov VASerezhenkov TIRomancova AFVanin 2013 16 In Russian * General aspects of muscle glucose uptake ROAlvim Annals of the Brazilian Academy of Sciences) 87 1 2015 Anais da Academia Brasileira de Ciências. In Portugal