<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">medsovet</journal-id><journal-title-group><journal-title xml:lang="ru">Медицинский Совет</journal-title><trans-title-group xml:lang="en"><trans-title>Meditsinskiy sovet = Medical Council</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2079-701X</issn><issn pub-type="epub">2658-5790</issn><publisher><publisher-name>REMEDIUM GROUP Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.21518/2079-701X-2020-21-160-168</article-id><article-id custom-type="elpub" pub-id-type="custom">medsovet-5980</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>Эндокринология</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>Endocrinology</subject></subj-group></article-categories><title-group><article-title>Сахарный диабет 2-го типа: терапевтические стратегии сахароснижающей терапии в свете доказательной медицины</article-title><trans-title-group xml:lang="en"><trans-title>Type 2 diabetes: evidence-based medicine approach to glucose-lowering therapy</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-9007-4123</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Бирюкова</surname><given-names>Е. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Biryukova</surname><given-names>E. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>д.м.н., профессор, профессор кафедры эндокринологии и диабетологии,</p><p>127473, Москва, ул. Делегатская, д. 20, стр. 1</p></bio><bio xml:lang="en"><p>Dr. of Sci. (Med.), Professor, Professor of Department of Endocrinology and Diabetology, </p><p>20, Bldg. 1, Delegatskaya St., Moscow, 127473</p></bio><email xlink:type="simple">lena@obsudim.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1939-261X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Морозова</surname><given-names>И. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Morozova</surname><given-names>I. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>к.м.н., старший научный сотрудник отдела эндокринных и метаболических заболеваний,</p><p>111123, Москва, шоссе Энтузиастов, д. 86</p></bio><bio xml:lang="en"><p>Cand. of Sci. (Med.), Senior Research Associate, Department of Endocrine and Metabolic Disorders, </p><p>86, Entuziastov Highway, Moscow, 111123</p></bio><email xlink:type="simple">I.morozova@mknc.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8851-2358</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Родионова</surname><given-names>С. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Rodionova</surname><given-names>S. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>врач-эндокринолог клиники женского здоровья, </p><p>111123, Москва, шоссе Энтузиастов, д. 86</p></bio><bio xml:lang="en"><p>Endocrinologist, Women’s Health Clinic, </p><p>86, Entuziastov Highway, Moscow, 111123</p></bio><email xlink:type="simple">s.rodionowa2011@yandex.ru</email><xref ref-type="aff" rid="aff-2"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Московский государственный медико-стоматологический университет им. А.И. Евдокимова</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Yevdokimov Moscow State University of Medicine and Dentistry</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Московский клинический научно-практический центр им. А.С. Логинова</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Loginov Moscow Clinical Scientific Centerof the Moscow Health Department</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2020</year></pub-date><pub-date pub-type="epub"><day>15</day><month>01</month><year>2021</year></pub-date><volume>0</volume><issue>21</issue><fpage>160</fpage><lpage>168</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Бирюкова Е.В., Морозова И.А., Родионова С.В., 2021</copyright-statement><copyright-year>2021</copyright-year><copyright-holder xml:lang="ru">Бирюкова Е.В., Морозова И.А., Родионова С.В.</copyright-holder><copyright-holder xml:lang="en">Biryukova E.V., Morozova I.A., Rodionova S.V.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.med-sovet.pro/jour/article/view/5980">https://www.med-sovet.pro/jour/article/view/5980</self-uri><abstract><p>Сахарный диабет 2-го типа является серьезной медико-социальной проблемой. Опасность заболевания связана с эпидемическими темпами роста и хроническими осложнениями, ведущими к ранней инвалидизации, снижению качества жизни и смертности населения. Основа профилактики диабетических осложнений – оптимальная сахароснижающая терапия с достижением целевых метаболических показателей с момента диагностики СД2 и в течение всей жизни пациента. Сложные патогенетические механизмы СД2 являются обоснованием для фармакотерапии с одновременным воздействием на различные нарушения, которая обеспечит больший сахароснижающий потенциал и поддержание эффективного контроля гликемии по мере прогрессирования СД2. Основные причины неудовлетворительного контроля заболевания включают клиническую инертность, несвоевременную интенсификацию фармакотерапии, использование схем лечения, недостаточно эффективных с учетом прогрессирующего течения заболевания. Лечение СД2 основано на клинических рекомендациях. Рассмотрены возможности патогенетической терапии, связанные с применением вилдаглиптина, метформина. Большое внимание в современной диабетологии придается изучению влияния различных терапевтических подходов на темпы прогрессирования заболевания с позиции улучшения прогноза и длительного сохранения целевого гликемического контроля. Рассматриваются преимущества комбинированной сахароснижающей терапии в дебюте СД2 по сравнению с поэтапной интенсификацией сахароснижающей терапии. В исследовании VERIFY изучалась долговременная эффективность и безопасность двух подходов к лечению: ранней комбинированной терапии метформином и вилдаглиптином в сравнении с традиционным поэтапным подходом с назначением метформина в качестве стартовой терапии. Комбинированная сахароснижающая терапия является важным направлением в терапии пациентов с впервые выявленным СД2.</p></abstract><trans-abstract xml:lang="en"><p>Type 2 diabetes mellitus is a serious medical and social problem. The danger of the disease is associated with epidemic growth rates and chronic complications, leading to early disability, decreased quality of life and mortality. The prevention of diabetes complications is based on the optimal glucose-lowering therapy with the achievement of target metabolic parameters from the date the diagnosis of T2DM was established and throughout the patient’s life. The complex pathogenetic mechanisms of T2DM are the underlying rationale for drug therapy with a simultaneous effect on various disorders, which will provide a greater hypoglycemic potential and maintain effective glycemic control as T2DM progresses. The main reasons for poor disease control include clinical inertia, untimely intensification of drug therapy, and the use of treatment regimens that are insufficiently effective given the progressive course of the disease. The therapy for T2DM is based on clinical guidelines. The pathogenetic therapy options associated with the use of vildagliptin and metformin are considered. Much attention in modern diabetology is paid to the study of the influence of various therapeutic approaches on the disease progression rates from the perspective of improving prognosis and long-term maintenance of target glycemic control. The advantages of combined glucose-lowering therapy at the onset of T2DM are considered in comparison with the stepwise intensification of glucose-lowering therapy. The VERIFY study examined the long-term efficacy and safety of two treatment approaches: early vildagliptin and metformin combination therapy versus the traditional stepwise approach starting with metformin as initial therapy. The combined glucose-lowering therapy is an important direction in the treatment of patients with newly diagnosed type 2 diabetes.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>сахарный диабет</kwd><kwd>гликированный гемоглобин (HbA1c)</kwd><kwd>хронические осложнения</kwd><kwd>вилдаглиптин</kwd><kwd>метформин</kwd><kwd>комбинированная сахароснижающая терапия</kwd><kwd>исследование VERIFY</kwd></kwd-group><kwd-group xml:lang="en"><kwd>diabetes mellitus</kwd><kwd>glycated hemoglobin (HbA1c)</kwd><kwd>chronic complications</kwd><kwd>vildagliptin</kwd><kwd>metformin</kwd><kwd>combined glucoselowering therapy</kwd><kwd>VERIFY study</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Dedov I., Shestakova M., Benedetti M.M., Simon D., Pakhomov I., Galstyan G. Prevalence of type 2 diabetes mellitus (T2DM) in the adult Russian population (NATION study). Diabetes Res Clin Pract. 2016;115:90–95. doi: 10.1016/j.diabres.2016.02.010.</mixed-citation><mixed-citation xml:lang="en">Dedov I., Shestakova M., Benedetti M.M., Simon D., Pakhomov I., Galstyan G. Prevalence of type 2 diabetes mellitus (T2DM) in the adult Russian population (NATION study). Diabetes Res Clin Pract. 2016;115:90–95. doi: 10.1016/j.diabres.2016.02.010.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Echouffo-Tcheugui J.B., Kengne A.P. On the importance of global cardiovascular risk assessment in people with type 2 diabetes. Prim Care Diabetes. 2013;7(2):95–102. doi: 10.1016/j.pcd.2013.03.002.</mixed-citation><mixed-citation xml:lang="en">Echouffo-Tcheugui J.B., Kengne A.P. On the importance of global cardiovascular risk assessment in people with type 2 diabetes. Prim Care Diabetes. 2013;7(2):95–102. doi: 10.1016/j.pcd.2013.03.002.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Papatheodorou K., Papanas N., Banach M., Papazoglou D., Edmonds M. Complications of Diabetes. J Diabetes Res. 2016;2016:6989453. doi: 10.1155/2016/6989453.</mixed-citation><mixed-citation xml:lang="en">Papatheodorou K., Papanas N., Banach M., Papazoglou D., Edmonds M. Complications of Diabetes. J Diabetes Res. 2016;2016:6989453. doi: 10.1155/2016/6989453.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Bloomgarden Z.T. Cardiovascular disease in diabetes. Diabetes Care. 2008;31(6):1260–1266. doi: 10.2337/dc08-zb06.</mixed-citation><mixed-citation xml:lang="en">Bloomgarden Z.T. Cardiovascular disease in diabetes. Diabetes Care. 2008;31(6):1260–1266. doi: 10.2337/dc08-zb06.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Holman R.R., Paul S.K., Bethel M.A., Matthews D.R., Neil H.A. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359(15):1577–1589. doi: 10.1056/nejmoa0806470.</mixed-citation><mixed-citation xml:lang="en">Holman R.R., Paul S.K., Bethel M.A., Matthews D.R., Neil H.A. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359(15):1577–1589. doi: 10.1056/nejmoa0806470.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Schwartz S.S., Epstein S., Corkey B.E., Grant S.F., Gavin J.R. 3rd, Aguilar R.B. 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):129–130. doi: 10.2337/dc15-1585.</mixed-citation><mixed-citation xml:lang="en">Schwartz S.S., Epstein S., Corkey B.E., Grant S.F., Gavin J.R. 3rd, Aguilar R.B. 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):129–130. doi: 10.2337/dc15-1585.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Shim W.S., Kim S.K., Kim H.J., Kang E.S., Ahn C.W., Lim S.K. et al. Decremental of postprandial insulin secretion determines the progressive nature of type-2 diabetes. Eur J Endocrinol. 2006;155(4):615–622. doi: 10.1530/eje.1.02249.</mixed-citation><mixed-citation xml:lang="en">Shim W.S., Kim S.K., Kim H.J., Kang E.S., Ahn C.W., Lim S.K. et al. Decremental of postprandial insulin secretion determines the progressive nature of type-2 diabetes. Eur J Endocrinol. 2006;155(4):615–622. doi: 10.1530/eje.1.02249.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Kahn S.E. The relative contributions of insulin resistance and ß-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia. 2003;46(1):3–19. doi: 10.1007/s00125-002-1009-0.</mixed-citation><mixed-citation xml:lang="en">Kahn S.E. The relative contributions of insulin resistance and ß-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia. 2003;46(1):3–19. doi: 10.1007/s00125-002-1009-0.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Yu S., Schwab P., Bian B., Radican L., Tunceli K. Use of Add-on Treatment to Metformin Monotherapy for Patients with Type 2 Diabetes and Suboptimal Glycemic Control: A U.S. Database Study. J Manag Care Spec Pharm. 2016;22(3):272–280. doi: 10.18553/jmcp.2016.22.3.272.</mixed-citation><mixed-citation xml:lang="en">Yu S., Schwab P., Bian B., Radican L., Tunceli K. Use of Add-on Treatment to Metformin Monotherapy for Patients with Type 2 Diabetes and Suboptimal Glycemic Control: A U.S. Database Study. J Manag Care Spec Pharm. 2016;22(3):272–280. doi: 10.18553/jmcp.2016.22.3.272.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Brown J.B., Conner C., Nichols G.A. Secondary failure of metformin monotherapy in clinical practice. Diabetes Care. 2010;33(3):501–506. doi: 10.2337/dc09-1749.</mixed-citation><mixed-citation xml:lang="en">Brown J.B., Conner C., Nichols G.A. Secondary failure of metformin monotherapy in clinical practice. Diabetes Care. 2010;33(3):501–506. doi: 10.2337/dc09-1749.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Moses R.G. Combination therapy for patients with type 2 diabetes: repaglinide in combination with metformin. Expert Rev Endocrinol Metab. 2010;5(3):331–342. doi: 10.1586/eem.10.17.</mixed-citation><mixed-citation xml:lang="en">Moses R.G. Combination therapy for patients with type 2 diabetes: repaglinide in combination with metformin. Expert Rev Endocrinol Metab. 2010;5(3):331–342. doi: 10.1586/eem.10.17.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Дедов И.И., Шестакова М.В., Майоров А.Ю. (ред.). Алгоритмы специализированной медицинской помощи больных сахарным диабетом. 9-й выпуск. Сахарный диабет. 2019;22(1S1):1–144. Режим доступа: https://diabetmed.net/wp-content/uploads/2019/12/12211-29550-6-PB.pdf.</mixed-citation><mixed-citation xml:lang="en">Dedov I.I., Shestakova M.V., Mayorov A.Yu. (eds.). Standards of specialized diabetes care. 9th ed. Sakharni Diabet = Diabetes Mellitus. 2019;22(1S1):1– 144. (In Russ.) Available at: https://diabetmed.net/wp-content/uploads/2019/12/12211-29550-6-PB.pdf.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Bianchi C., Daniele G., Dardano A., Miccoli R., Del Prato S. Early combination therapy with oral glucose-lowering agents in type 2 diabetes. Drugs. 2017;77(3):247–264. doi: 10.1007/s40265-017-0694-4.</mixed-citation><mixed-citation xml:lang="en">Bianchi C., Daniele G., Dardano A., Miccoli R., Del Prato S. Early combination therapy with oral glucose-lowering agents in type 2 diabetes. Drugs. 2017;77(3):247–264. doi: 10.1007/s40265-017-0694-4.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Liu Y., Hong T. Combination therapy of dipeptidyl peptidase-4 inhibitors and metformin in type 2 diabetes: rationale and evidence. Diabetes Obes Metab. 2014;16(2):111–117. doi: 10.1111/dom.12128.</mixed-citation><mixed-citation xml:lang="en">Liu Y., Hong T. Combination therapy of dipeptidyl peptidase-4 inhibitors and metformin in type 2 diabetes: rationale and evidence. Diabetes Obes Metab. 2014;16(2):111–117. doi: 10.1111/dom.12128.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Дедов И.И., Шестакова М.В. Феномен «метаболической памяти» в прогнозировании риска развития сосудистых осложнений при сахарном диабете. Терапевтический архив. 2015;87(10):4–10. doi: 10.17116/terarkh201587104-10.</mixed-citation><mixed-citation xml:lang="en">Dedov I.I., Shestakova M.V. The metabolic memory phenomenon in predicting a risk for vascular complications in diabetes mellitus. Terapevticheskiy arkhiv = Therapeutic Archive. 2015;87(10):4–10. (In Russ.) doi: 10.17116/terarkh201587104-10.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Ceriello A., Ihnat M.A., Thorpe J.E. The metabolic memory: is more than just tight glucose control nessesary to prevent diabetic complications? J Clin Metab. 2009;94(2):410–415. doi: 10.1210/jc.2008-1824.</mixed-citation><mixed-citation xml:lang="en">Ceriello A., Ihnat M.A., Thorpe J.E. The metabolic memory: is more than just tight glucose control nessesary to prevent diabetic complications? J Clin Metab. 2009;94(2):410–415. doi: 10.1210/jc.2008-1824.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Phung O.J., Sobieraj D.M., Engel S.S., Rajpathak S.N. Early combination therapy for the treatment of type 2 diabetes mellitus: systematic review and metaanalysis. Diabetes Obes Metab. 2014;16(5):410–417. doi: 10.1111/dom.12233.</mixed-citation><mixed-citation xml:lang="en">Phung O.J., Sobieraj D.M., Engel S.S., Rajpathak S.N. Early combination therapy for the treatment of type 2 diabetes mellitus: systematic review and metaanalysis. Diabetes Obes Metab. 2014;16(5):410–417. doi: 10.1111/dom.12233.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Rozenfeld Y., Hunt J.S., Plauschinat C., Wong K.S. Oral antidiabetic medication adherence and glycemic control in managed care. Am J Manag Care. 2008;14:71–75. Available at: https://www.ajmc.com/journals/issue/2008/2008-02-vol14-n2/feb08-2832p071-075.</mixed-citation><mixed-citation xml:lang="en">Rozenfeld Y., Hunt J.S., Plauschinat C., Wong K.S. Oral antidiabetic medication adherence and glycemic control in managed care. Am J Manag Care. 2008;14:71–75. Available at: https://www.ajmc.com/journals/issue/2008/2008-02-vol14-n2/feb08-2832p071-075.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Khunti N., Khunti N., Khunti K. Adherence to type 2 diabetes management Br J Diabetes. 2019;19(2):99–104. doi: 10.15277/bjd.2019.223.</mixed-citation><mixed-citation xml:lang="en">Khunti N., Khunti N., Khunti K. Adherence to type 2 diabetes management Br J Diabetes. 2019;19(2):99–104. doi: 10.15277/bjd.2019.223.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Tahrani A.A., Piya M.K., Barnet A.H. Drug evaluation: vildagliptin-metformin single-tablet combination. Adv Ther. 2009;26(20):138–154. doi: 10.1007/s12325-009-0010-0.</mixed-citation><mixed-citation xml:lang="en">Tahrani A.A., Piya M.K., Barnet A.H. Drug evaluation: vildagliptin-metformin single-tablet combination. Adv Ther. 2009;26(20):138–154. doi: 10.1007/s12325-009-0010-0.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Cai L., Cai Y., Lu Z.J., Zhang Y., Liu P. The efficacy and safety of vildagliptin in patients with type 2 diabetes: a meta-analysis of randomized clinical trials. J Clin Pharm Ther. 2012;37(4):386–398. doi: 10.1111/j.1365-2710.2011.01323.x.</mixed-citation><mixed-citation xml:lang="en">Cai L., Cai Y., Lu Z.J., Zhang Y., Liu P. The efficacy and safety of vildagliptin in patients with type 2 diabetes: a meta-analysis of randomized clinical trials. J Clin Pharm Ther. 2012;37(4):386–398. doi: 10.1111/j.1365-2710.2011.01323.x.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">McInnes G., Evans M., Del Prato S., Stumvoll M., Schweizer A., Lukashevich V. et al. Cardiovascular and heart failure safety profile of vildagliptin: a metaanalysis of 17 000 patients. Diabetes Obes Metab. 2015;17(11):1085–1092. doi: 10.1111/dom.12548.</mixed-citation><mixed-citation xml:lang="en">McInnes G., Evans M., Del Prato S., Stumvoll M., Schweizer A., Lukashevich V. et al. Cardiovascular and heart failure safety profile of vildagliptin: a metaanalysis of 17 000 patients. Diabetes Obes Metab. 2015;17(11):1085–1092. doi: 10.1111/dom.12548.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Rojas L.B., Gomes M.B. Metformin: an old but still the best treatment for type 2 diabetes Diabetol Metab Syndr. 2013;5(1):6. doi: 10.1186/1758-5996-5-6.</mixed-citation><mixed-citation xml:lang="en">Rojas L.B., Gomes M.B. Metformin: an old but still the best treatment for type 2 diabetes Diabetol Metab Syndr. 2013;5(1):6. doi: 10.1186/1758-5996-5-6.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Markowicz-Piasecka M., Huttunen K.M., Mateusiak L., Mikiciuk-Olasik E., Sikora J. Is Metformin a Perfect Drug? Updates in Pharmacokinetics and Pharmacodynamics. Curr Pharm Des. 2017;23(17):2532–2550.doi: 10.2174/1381612822666161201152941.</mixed-citation><mixed-citation xml:lang="en">Markowicz-Piasecka M., Huttunen K.M., Mateusiak L., Mikiciuk-Olasik E., Sikora J. Is Metformin a Perfect Drug? Updates in Pharmacokinetics and Pharmacodynamics. Curr Pharm Des. 2017;23(17):2532–2550.doi: 10.2174/1381612822666161201152941.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Schweizer A., Couturier A., Foley J.E., Dejager S. Comparison between vildagliptin and metformin to sustain reduction in HbA1c over 1 year in drugnaive patients with type 2 Diabetes. Diabet Med. 2007;24(9):955–961. doi: 10.1111/j.1464-5491.2007.02191.x.</mixed-citation><mixed-citation xml:lang="en">Schweizer A., Couturier A., Foley J.E., Dejager S. Comparison between vildagliptin and metformin to sustain reduction in HbA1c over 1 year in drugnaive patients with type 2 Diabetes. Diabet Med. 2007;24(9):955–961. doi: 10.1111/j.1464-5491.2007.02191.x.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Pratley R.E., Salsali A. Inhibition of DPP-4: a new therapeutic approach for the treatment of type 2 diabetes. Curr Med Res Opin. 2007;23(4):919–931. doi: 10.1185/030079906x162746.</mixed-citation><mixed-citation xml:lang="en">Pratley R.E., Salsali A. Inhibition of DPP-4: a new therapeutic approach for the treatment of type 2 diabetes. Curr Med Res Opin. 2007;23(4):919–931. doi: 10.1185/030079906x162746.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Aroda V.R., Henry R.R., Han J., Huang W., DeYoung M.B., Darsow T., Hoogwerf B.J. Efficacy of GLP-1 receptor agonists and DPP-4 inhibitors: Meta-analysis and systematic review. Clin Ther. 2012;34(6):1247–1258.e22. doi: 10.1016/j.clinthera.2012.04.013.</mixed-citation><mixed-citation xml:lang="en">Aroda V.R., Henry R.R., Han J., Huang W., DeYoung M.B., Darsow T., Hoogwerf B.J. Efficacy of GLP-1 receptor agonists and DPP-4 inhibitors: Meta-analysis and systematic review. Clin Ther. 2012;34(6):1247–1258.e22. doi: 10.1016/j.clinthera.2012.04.013.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Deacon C.F., Holst J.J. Dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes: comparison, efficacy and safety. Expert Opin Pharmacother. 2013;14(15):2047–2058. doi: 10.1517/14656566.2013.824966.</mixed-citation><mixed-citation xml:lang="en">Deacon C.F., Holst J.J. Dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes: comparison, efficacy and safety. Expert Opin Pharmacother. 2013;14(15):2047–2058. doi: 10.1517/14656566.2013.824966.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">DeFronzo R.A. Current issues in the treatment of type 2 diabetes. Overview of newer agents: where treatment is going. Am J Med. 2010;123(3 Suppl):S38–S48. doi: 10.1016/j.amjmed.2009.12.008.</mixed-citation><mixed-citation xml:lang="en">DeFronzo R.A. Current issues in the treatment of type 2 diabetes. Overview of newer agents: where treatment is going. Am J Med. 2010;123(3 Suppl):S38–S48. doi: 10.1016/j.amjmed.2009.12.008.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Liu Y., Hong T. Combination therapy of dipeptidyl peptidase-4 inhibitors and metformin in type 2 diabetes: rationale and evidence. Diabetes Obes Metab. 2014;16(2):111–117. doi: 10.1111/dom.12128.</mixed-citation><mixed-citation xml:lang="en">Liu Y., Hong T. Combination therapy of dipeptidyl peptidase-4 inhibitors and metformin in type 2 diabetes: rationale and evidence. Diabetes Obes Metab. 2014;16(2):111–117. doi: 10.1111/dom.12128.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Balas B., Baig M.R., Watson C., Dunning B.E., Ligueros-Saylan M., Wang Y. et al. The dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after single-dose administration in type 2 diabetic patients. J Clin Endocrinol Metab. 2007;92(4):1249–1255. doi: 10.1210/jc.2006-1882.</mixed-citation><mixed-citation xml:lang="en">Balas B., Baig M.R., Watson C., Dunning B.E., Ligueros-Saylan M., Wang Y. et al. The dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after single-dose administration in type 2 diabetic patients. J Clin Endocrinol Metab. 2007;92(4):1249–1255. doi: 10.1210/jc.2006-1882.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Samraj G.P. Vildagliptin for the treatment of diabetes. Therapy. 2011;8(6):703–719. Available at: https://www.openaccessjournals.com/articles/vildagliptin-for-the-treatment-of-diabetes.pdf.</mixed-citation><mixed-citation xml:lang="en">Samraj G.P. Vildagliptin for the treatment of diabetes. Therapy. 2011;8(6):703–719. Available at: https://www.openaccessjournals.com/articles/vildagliptin-for-the-treatment-of-diabetes.pdf.</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Chon S., Gautier J.F. An Update on the Effect of Incretin-Based Therapies on β-Cell Function and Mass. Diabetes Metab J. 2016;40(2):99–114. doi: 10.4093/dmj.2016.40.2.99.</mixed-citation><mixed-citation xml:lang="en">Chon S., Gautier J.F. An Update on the Effect of Incretin-Based Therapies on β-Cell Function and Mass. Diabetes Metab J. 2016;40(2):99–114. doi: 10.4093/dmj.2016.40.2.99.</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Kim N.H., Yu T., Lee D.H. The nonglycemic actions of dipeptidyl peptidase-4 inhibitors. Biomed Res Int. 2014;2014:368703. doi: 10.1155/2014/368703.</mixed-citation><mixed-citation xml:lang="en">Kim N.H., Yu T., Lee D.H. The nonglycemic actions of dipeptidyl peptidase-4 inhibitors. Biomed Res Int. 2014;2014:368703. doi: 10.1155/2014/368703.</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Chrysant S.G., Chrysant G.S. Clinical implications of cardiovascular preventing pleiotropic effects of dipeptidyl peptidase-4 inhibitors. Am J Cardiol. 2012;109(11):1681–1685. doi: 10.1016/j.amjcard.2012.01.398.</mixed-citation><mixed-citation xml:lang="en">Chrysant S.G., Chrysant G.S. Clinical implications of cardiovascular preventing pleiotropic effects of dipeptidyl peptidase-4 inhibitors. Am J Cardiol. 2012;109(11):1681–1685. doi: 10.1016/j.amjcard.2012.01.398.</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Rena G., Hardie G.G., Pearson E.A. The mechanisms of action of metformin. Diabetologia. 2017;60(9):1577–1585. doi: 10.1007/s00125-017-4342-z.</mixed-citation><mixed-citation xml:lang="en">Rena G., Hardie G.G., Pearson E.A. The mechanisms of action of metformin. Diabetologia. 2017;60(9):1577–1585. doi: 10.1007/s00125-017-4342-z.</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">McFarlane S.I., Banerji M., Sowers J.R. Insulin resistance and cardiovascular disease. J Clin Endocrinol Metab. 2001;86(2):713–718. doi: 10.1210/jcem.86.2.7202.</mixed-citation><mixed-citation xml:lang="en">McFarlane S.I., Banerji M., Sowers J.R. Insulin resistance and cardiovascular disease. J Clin Endocrinol Metab. 2001;86(2):713–718. doi: 10.1210/jcem.86.2.7202.</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Ormazabal V., Nair S., Elfeky O., Aguayo C., Salomon C., Zuñiga F.A. Association between insulin resistance and the development of cardiovascular disease. Cardiovasc Diabetol. 2018;17(1):122. 10.1186/s12933-018-0762-4.</mixed-citation><mixed-citation xml:lang="en">Ormazabal V., Nair S., Elfeky O., Aguayo C., Salomon C., Zuñiga F.A. Association between insulin resistance and the development of cardiovascular disease. Cardiovasc Diabetol. 2018;17(1):122. 10.1186/s12933-018-0762-4.</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Towler M.C., Hardie D.G. AMP-Activated protein kinase in metabolic control and insulin signaling. Circ Res. 2007;100(3):328–341. doi: 10.1161/01. RES.0000256090.42690.05.</mixed-citation><mixed-citation xml:lang="en">Towler M.C., Hardie D.G. AMP-Activated protein kinase in metabolic control and insulin signaling. Circ Res. 2007;100(3):328–341. doi: 10.1161/01. RES.0000256090.42690.05.</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">He L., Sabet A., Djedjos S., Miller R., Sun X., Hussain M.A. et al. Metformin and insulin suppress hepatic gluconeogenesis through phosphorylation of CREB binding protein. Cell. 2009;137(4):635–646. doi: 10.1016/j.cell.2009.03.016.</mixed-citation><mixed-citation xml:lang="en">He L., Sabet A., Djedjos S., Miller R., Sun X., Hussain M.A. et al. Metformin and insulin suppress hepatic gluconeogenesis through phosphorylation of CREB binding protein. Cell. 2009;137(4):635–646. doi: 10.1016/j.cell.2009.03.016.</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">McCreight L.J., Bailey C.J., Pearson E.R. Metformin and the gastrointestinal tract. Diabetologia. 2016;59(3):426–435. doi: 10.1007/s00125-015-3844-9.</mixed-citation><mixed-citation xml:lang="en">McCreight L.J., Bailey C.J., Pearson E.R. Metformin and the gastrointestinal tract. Diabetologia. 2016;59(3):426–435. doi: 10.1007/s00125-015-3844-9.</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">Preiss D., Dawed A., Welsh P., Heggie A., Jones A.G., Dekker J. et al. Sustained influence of metformin therapy on circulating glucagon-like peptide-1 levels inindividuals with and without type 2 diabetes. Diabetes Obes Metab. 2017;19(3):356–363. doi: 10.1111/dom.12826.</mixed-citation><mixed-citation xml:lang="en">Preiss D., Dawed A., Welsh P., Heggie A., Jones A.G., Dekker J. et al. Sustained influence of metformin therapy on circulating glucagon-like peptide-1 levels inindividuals with and without type 2 diabetes. Diabetes Obes Metab. 2017;19(3):356–363. doi: 10.1111/dom.12826.</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">DeFronzo R.A., Buse J.B., Kim T., Burns C., Skare S., Baron A., Fineman M. Once-daily delayed-release metformin lowers plasma glucose and enhances fasting and postprandial GLP-1 and PYY: results from two randomised trials. Diabetologia. 2016;59(8):1645–1654. doi: 10.1007/s00125-016-3992-6.</mixed-citation><mixed-citation xml:lang="en">DeFronzo R.A., Buse J.B., Kim T., Burns C., Skare S., Baron A., Fineman M. Once-daily delayed-release metformin lowers plasma glucose and enhances fasting and postprandial GLP-1 and PYY: results from two randomised trials. Diabetologia. 2016;59(8):1645–1654. doi: 10.1007/s00125-016-3992-6.</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru">Hinke S.A., Kühn-Wache K., Hoffmann T., Pederson R.A., McIntosh C.H., Demuth H.U. Metformin effects on dipeptidylpeptidase IV degradation of glucagon-like peptide-1. Biochem Biophys Res Commun. 2002;291(5):1302–1308. doi: 10.1006/bbrc.2002.6607.</mixed-citation><mixed-citation xml:lang="en">Hinke S.A., Kühn-Wache K., Hoffmann T., Pederson R.A., McIntosh C.H., Demuth H.U. Metformin effects on dipeptidylpeptidase IV degradation of glucagon-like peptide-1. Biochem Biophys Res Commun. 2002;291(5):1302–1308. doi: 10.1006/bbrc.2002.6607.</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">Lien F., Berthier A., Bouchaert E., Gheeraert C., Alexandre J., Porez G. et al. Metformin interferes with bile acid homeostasis through AMPK–FXR crosstalk. J Clin Invest. 2014;124(3):1037–1051. doi: 10.1172/JCI68815.</mixed-citation><mixed-citation xml:lang="en">Lien F., Berthier A., Bouchaert E., Gheeraert C., Alexandre J., Porez G. et al. Metformin interferes with bile acid homeostasis through AMPK–FXR crosstalk. J Clin Invest. 2014;124(3):1037–1051. doi: 10.1172/JCI68815.</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">Scarpello J.H. Improving survival with metformin: the evidence base today. Diabetes Metab. 2003;29(4 Pt 2):6S36–6S43. doi: 10.1016/s1262-3636(03)72786-4.</mixed-citation><mixed-citation xml:lang="en">Scarpello J.H. Improving survival with metformin: the evidence base today. Diabetes Metab. 2003;29(4 Pt 2):6S36–6S43. doi: 10.1016/s1262-3636(03)72786-4.</mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">Holden S.E., Jenkins-Jones S., Currie C.J. Association between Insulin Monotherapy versus Insulin plus Metformin and the Risk of All-Cause Mortality and Other Serious Outcomes: A Retrospective Cohort Study. PLoS One. 2016;11(5):e0153594. doi: 10.1371/journal.pone.0153594.</mixed-citation><mixed-citation xml:lang="en">Holden S.E., Jenkins-Jones S., Currie C.J. Association between Insulin Monotherapy versus Insulin plus Metformin and the Risk of All-Cause Mortality and Other Serious Outcomes: A Retrospective Cohort Study. PLoS One. 2016;11(5):e0153594. doi: 10.1371/journal.pone.0153594.</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru">Nesti L, Natali A. Metformin effects on the heart and the cardiovascular system: A review of experimental and clinical data. Nutr Metab Cardiovasc Dis. 2017;27(8):657–669. doi: 10.1016/j.numecd.2017.04.009.</mixed-citation><mixed-citation xml:lang="en">Nesti L, Natali A. Metformin effects on the heart and the cardiovascular system: A review of experimental and clinical data. Nutr Metab Cardiovasc Dis. 2017;27(8):657–669. doi: 10.1016/j.numecd.2017.04.009.</mixed-citation></citation-alternatives></ref><ref id="cit49"><label>49</label><citation-alternatives><mixed-citation xml:lang="ru">Del Prato S., Foley J.E., Kothny W., Kozlovski P., Stumvoll M., Paldánius P.M., Matthews D.R. Study to determine the durability of glycaemic control with early treatment with a vildagliptin-metformin combination regimen vs. standard-of-care metformin monotherapy-the VERIFY trial: a randomized double-blind trial. Diabet Med. 2011;31(10):1178–1184. doi: 10.1111/dme.12508.</mixed-citation><mixed-citation xml:lang="en">Del Prato S., Foley J.E., Kothny W., Kozlovski P., Stumvoll M., Paldánius P.M., Matthews D.R. Study to determine the durability of glycaemic control with early treatment with a vildagliptin-metformin combination regimen vs. standard-of-care metformin monotherapy-the VERIFY trial: a randomized double-blind trial. Diabet Med. 2011;31(10):1178–1184. doi: 10.1111/dme.12508.</mixed-citation></citation-alternatives></ref><ref id="cit50"><label>50</label><citation-alternatives><mixed-citation xml:lang="ru">Matthews D.R., Paldánius P.M., Proot P., Foley J.E., Stumvoll M., Del Prato S. Baseline characteristics in the VERIFY study: a randomized trial assessing the durability of glycaemic control with early vildagliptin-metformin combination in newly diagnosed Type 2 diabetes. Diabet Med. 2019;36(4):505– 513. doi: 10.1111/dme.13886.</mixed-citation><mixed-citation xml:lang="en">Matthews D.R., Paldánius P.M., Proot P., Foley J.E., Stumvoll M., Del Prato S. Baseline characteristics in the VERIFY study: a randomized trial assessing the durability of glycaemic control with early vildagliptin-metformin combination in newly diagnosed Type 2 diabetes. Diabet Med. 2019;36(4):505– 513. doi: 10.1111/dme.13886.</mixed-citation></citation-alternatives></ref><ref id="cit51"><label>51</label><citation-alternatives><mixed-citation xml:lang="ru">Matthews D.R., Paldánius P.M., Proot P., Chiang Y., Stumvoll M., Del Prato S. Glycaemic durability of an early combination therapy with vildagliptin and metformin versus sequential metformin monotherapy in newly diagnosed type 2 diabetes (VERIFY): a 5-year, multicentre, randomised, double-blind trial. Lancet. 2019;394(10208):1519–1529. doi: 10.1016/S0140-6736(19)32131-2.</mixed-citation><mixed-citation xml:lang="en">Matthews D.R., Paldánius P.M., Proot P., Chiang Y., Stumvoll M., Del Prato S. Glycaemic durability of an early combination therapy with vildagliptin and metformin versus sequential metformin monotherapy in newly diagnosed type 2 diabetes (VERIFY): a 5-year, multicentre, randomised, double-blind trial. Lancet. 2019;394(10208):1519–1529. doi: 10.1016/S0140-6736(19)32131-2.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
