<?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">nogr</journal-id><journal-title-group><journal-title xml:lang="ru">Экспериментальная и клиническая гастроэнтерология</journal-title><trans-title-group xml:lang="en"><trans-title>Experimental and Clinical Gastroenterology</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1682-8658</issn><publisher><publisher-name>«Global Media Technologies»</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.31146/1682-8658-ecg-194-10-82-90</article-id><article-id custom-type="elpub" pub-id-type="custom">nogr-1763</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>КЛИНИЧЕСКАЯ ГАСТРОЭНТЕРОЛОГИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>CLINICAL GASTROENTEROLOGY</subject></subj-group></article-categories><title-group><article-title>Прямое сравнение эффектов лираглутида и дулаглутида на динамику шкал и маркеров печеночного фиброза</article-title><trans-title-group xml:lang="en"><trans-title>Direct comparison of the effects of liraglutide and dulaglutide on the dynamics of scales and markers of hepatic fibrosis</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1414-0034</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Мартьянова</surname><given-names>М. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Martianova</surname><given-names>M. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Мартьянова Мария Владимировна - аспирант кафедры эндокринологии, врач-эндокринолог высшей категории.</p><p>197341, Санкт-Петербург, ул. Аккуратова, д. 2.</p></bio><bio xml:lang="en"><p>Mariia V. Martianova - postgraduate of endocrinology department, MD, doctor endocrinologist.</p><p>2 Akkuratova street, St. Petersburg, 197341.</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-0837-8385</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Лаевская</surname><given-names>М. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Laevskaya</surname><given-names>M. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Лаевская Мария Юрьевна – кандидат медицинских наук, старший научный сотрудник Научно-Исследовательской Лаборатории диабетологии Института эндокринологии, доцент кафедры эндокринологии Института медицинского образования.</p><p>197341, Санкт-Петербург, ул. Аккуратова, д. 2.</p></bio><bio xml:lang="en"><p>Mariia Yu. Laevskaya - Candidate of Medical Sciences, Associate Professor Endocrinology Department of the Institute of Medical Education, Senior Researcher at the Research Laboratory of Diabetology of the Institute of Endocrinology.</p><p>2 Akkuratova street, St. Petersburg, 197341.</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5149-4667</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Мелтонян</surname><given-names>А. Р.</given-names></name><name name-style="western" xml:lang="en"><surname>Meltonian</surname><given-names>A. R.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Мелтонян Ася Робертовна - аспирант кафедры эндокринологии, врач-эндокринолог.</p><p>197341, Санкт-Петербург, ул. Аккуратова, д. 2.</p></bio><bio xml:lang="en"><p>Asia R. Meltonian - postgraduate of endocrinology department, MD, doctor endocrinologist.</p><p>2 Akkuratova street, St. Petersburg, 197341.</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5285-8303</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Бреговский</surname><given-names>В. Б.</given-names></name><name name-style="western" xml:lang="en"><surname>Bregovskiy</surname><given-names>V. B.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Бреговский Вадим Борисович – доктор медицинских наук, врач-подиатр СПб Территориального диабетологического центра, СПб ГБУЗ ГКДЦ №1.</p><p>197341, Санкт-Петербург, ул. Аккуратова, д. 2.</p></bio><bio xml:lang="en"><p>Vadim B. Bregovskiy - Dr. of Sci. (Med), Doctor podiatrist Saint-Petersburg City Diabetes Centre.</p><p>2 Akkuratova street, St. Petersburg, 197341.</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0559-697X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Бабенко</surname><given-names>А. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Babenko</surname><given-names>A. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Бабенко Алина Юрьевна – доктор медицинских наук, заведующий НИО генетических рисков и персонифицированной профилактики НЦМУ ЦПМ, профессор кафедры эндокринологии Института медицинского образования, главный научный сотрудник Научно-Исследовательской Лабораторией диабетологии Института эндокринологии, врач-эндокринолог высшей категории.</p><p>197341, Санкт-Петербург, ул. Аккуратова, д. 2.</p></bio><bio xml:lang="en"><p>Alina Yu. Babenko - Dr. of Sci. (Med)., Professor of Endocrinology Department of the Institute of Medical Education, Leading Researcher, Head of Diabetology of the Institute of Endocrinology.</p><p>2 Akkuratova street, St. Petersburg, 197341.</p></bio><email xlink:type="simple">alina_babenko@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Национальный медицинский исследовательский центр имени В.А. Алмазова Министерства здравоохранения Российской Федерации</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Almazov National Medical Research Centre</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2021</year></pub-date><pub-date pub-type="epub"><day>23</day><month>12</month><year>2021</year></pub-date><volume>0</volume><issue>10</issue><fpage>82</fpage><lpage>90</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Мартьянова М.В., Лаевская М.Ю., Мелтонян А.Р., Бреговский В.Б., Бабенко А.Ю., 2021</copyright-statement><copyright-year>2021</copyright-year><copyright-holder xml:lang="ru">Мартьянова М.В., Лаевская М.Ю., Мелтонян А.Р., Бреговский В.Б., Бабенко А.Ю.</copyright-holder><copyright-holder xml:lang="en">Martianova M.V., Laevskaya M.Y., Meltonian A.R., Bregovskiy V.B., Babenko A.Y.</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.nogr.org/jour/article/view/1763">https://www.nogr.org/jour/article/view/1763</self-uri><abstract><sec><title>Цель работы</title><p>Цель работы. Сравнение эффектов лираглутида и дулаглутида на динамику шкал и маркеров печеночного фиброза.</p></sec><sec><title>Материалы и методы</title><p>Материалы и методы. 35 пациентов с НАЖБП были включены в исследование и получали лираглутид в дозе 1,8 мг или дулаглутид в дозе 1,5 мг один раз в день в течение 6 месяцев.</p></sec><sec><title>Результаты</title><p>Результаты. Масса тела и гликированный гемоглобин (HbA1C) значимо и сопоставимо снизились через 6 месяцев лечения в обеих группах. Только в группе лираглутида отмечено значимое снижение уровня инсулина и гликемии натощак. Сывороточный уровень аспартатаминотрансферазы (АСТ) снизился только в группе дулаглутида. Снижение уровня АСТ в группе дулаглутида составило с 31,9±26,8 до 30,8±10,6 Ед/л (р=0,04). Динамика риска фиброза достигла статистической значимости лишь при оценке по шкале FIB-4 в группе лираглутида при сравнении исходных значений и значений через 6 месяцев лечения — 1,18±0,51 и 0,97±0,40, соответственно (p=0.022). В группе дулаглутида так же отмечалась незначимая положительная динамика 1,31 ± 0,53 и 1,11 ± 0,23 (p=0,865).</p></sec><sec><title>Выводы</title><p>Выводы. Проведенное исследование продемонстрировало положительные эффекты лираглутида и дулаглутида на метаболические параметры и преимущество лираглутида по влиянию на динамку риска фиброза, оцененного по шкале FIB-4. В нашем исследовании не получено динамики по маркерам фиброза через 6 месяцев лечения ни в одной из групп. Для однозначного подтверждения преимуществ лираглутида в лечении пациентов с НАЖБП необходимы рандомизированные проспективные сравнительные исследования различных арГПП1 на больших выборках пациентов с различными стадиями НАЖБП.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Objective</title><p>Objective. Comparison of the effects of liraglutide and dulaglutide on the dynamics of scales and markers of hepatic fibrosis.</p></sec><sec><title>Materials and methods</title><p>Materials and methods. 35 patients with NAFLD were included in the study and received liraglutide 1.8 mg or dulaglutide 1.5 mg once daily for 6 months.</p></sec><sec><title>Results</title><p>Results. Body weight and glycated hemoglobin (HbA1C) decreased significantly and comparable after 6 months of treatment in both groups. Serum aspartate aminotransferase (AST) levels decreased only in the dulaglutide group. The decrease in the AST level in the dulaglutide group was from 31.9 ± 26.8 to 30.8 ± 10.6 U / L (p = 0.04). The dynamics of the risk of fibrosis reached statistical significance only when assessed on the FIB-4 scale in the liraglutide group when comparing the baseline values and values after 6 months of treatment — 1.18 ± 0.51 and 0.97 ± 0.40, respectively (p = 0.022). In the dulaglutide group, there was also an insignificant positive dynamics of 1.31 ± 0.53 and 1.11 ± 0.23 (p = 0.865), which can be explained by the minimal severity of changes at baseline.</p></sec><sec><title>Conclusions</title><p>Conclusions. The study demonstrated comparable effects of liraglutide and dulaglutide on metabolic parameters and, at the same time, the advantage of liraglutide in influencing the dynamics of the risk of fibrosis, assessed on the FIB-4 scale. To unequivocally confirm the benefits of liraglutide in the treatment of patients with NAFLD, randomized prospective comparative studies of various aGPP1 on large samples of patients with different stages of NAFLD are needed.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>Неалкогольная жировая болезнь печени</kwd><kwd>сахарный диабет 2 типа</kwd><kwd>агонисты рецепторов глюкагоноподобного пептида-1</kwd><kwd>ожирение</kwd><kwd>галектин-3</kwd><kwd>маркеры фиброза</kwd></kwd-group><kwd-group xml:lang="en"><kwd>Non-alcoholic fatty liver disease</kwd><kwd>type 2 diabetes mellitus</kwd><kwd>glucagon-like peptide-1 receptor agonists</kwd><kwd>obesity</kwd><kwd>galectin-3</kwd><kwd>fibrosis markers</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Исследование выполнено при финансовой поддержке Государственного задания «Оптимизация терапевтических подходов у пациентов с сахарным диабетом 2 типа и неалкогольной жировой болезнью печени».</funding-statement><funding-statement xml:lang="en">The study was carried out with the financial support of the State Task “Optimization of therapeutic approaches in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease”.</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Лазебник Л. Б., Голованова Е. В., Туркина С. В., и соавт. Неалкогольная жировая болезнь печени у взрослых: клиника, диагностика, лечение. Рекомендации для терапевтов, третья версия. Экспериментальная и клиническая гастроэнтерология. 2021;185(1): 4-52. DOI: 10.31146/1682-8658-ecg-185-1-4-52</mixed-citation><mixed-citation xml:lang="en">Lazebnik L.B., Golovanova E. V., Turkina S. V., et al. Nonalcoholic fatty liver disease in adults: clinic, diagnostics, treatment. Guidelines for therapists, third version. Experimental and Clinical Gastroenterology. 2021;1(1):4-52. (In Russ.) doi: 10.31146/1682-8658-ecg-185-1-4-52.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Friedman S.L., Ratziu V., Harrison S. A., et al. A randomized, placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis. Hepatology. 2018;67(5):1754-1767. doi: 10.1002/hep.29477.</mixed-citation><mixed-citation xml:lang="en">Friedman S.L., Ratziu V., Harrison S. A., et al. A randomized, placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis. Hepatology. 2018;67(5):1754-1767. doi: 10.1002/hep.29477.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Ивашкин В. Т., Драпкина О. М., Маев И. В., и соавт. Распространенность неалкогольной жировой болезни печени у пациентов амбулаторно-поликлинической практики в Российской Федерации: результаты исследования DIREG 2. Российский журнал гастроэнтерологии гепатологии колопроктологии. 2015;25(6):31-41.</mixed-citation><mixed-citation xml:lang="en">Ивашкин В. Т., Драпкина О. М., Маев И. В., и соавт. Распространенность неалкогольной жировой болезни печени у пациентов амбулаторно-поликлинической практики в Российской Федерации: результаты исследования DIREG 2. Российский журнал гастроэнтерологии гепатологии колопроктологии. 2015;25(6):31-41.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Lazo M., Clark J. M. The epidemiology of nonalcoholic fatty liver disease: a global perspective. Seminars in Liver Disease. 2008;28(4):339-350. doi: 10.1055/s-0028-1091978.</mixed-citation><mixed-citation xml:lang="en">Lazo M., Clark J. M. The epidemiology of nonalcoholic fatty liver disease: a global perspective. Seminars in Liver Disease. 2008;28(4):339-350. doi: 10.1055/s-0028-1091978.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Kim D.Y., Han K. H. Epidemiology and surveillance of hepatocellular carcinoma. Liver Cancer. 2012;1(1):2-14. doi: 10.1159/000339016.</mixed-citation><mixed-citation xml:lang="en">Kim D.Y., Han K. H. Epidemiology and surveillance of hepatocellular carcinoma. Liver Cancer. 2012;1(1):2-14. doi: 10.1159/000339016.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Budd J., Cusi K. Role of agents for the treatment of diabetes in the management of nonalcoholic fatty liver disease. Current Diabetes Reports. 2020;20(11):59. doi: 10.1007/s11892-020-01349-1.</mixed-citation><mixed-citation xml:lang="en">Budd J., Cusi K. Role of agents for the treatment of diabetes in the management of nonalcoholic fatty liver disease. Current Diabetes Reports. 2020;20(11):59. doi: 10.1007/s11892-020-01349-1.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Targher G. Editorial: A diabetologist's perspective on the diagnosis and monitoring of NAFLD. Alimentary Pharmacology &amp; Th erapeutics. 2020;52(4):710-711. doi: 10.1111/apt.15906.</mixed-citation><mixed-citation xml:lang="en">Targher G. Editorial: A diabetologist's perspective on the diagnosis and monitoring of NAFLD. Alimentary Pharmacology &amp; Th erapeutics. 2020;52(4):710-711. doi: 10.1111/apt.15906.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Mahfood Haddad T., Hamdeh S., Kanmanthareddy A., et al. Nonalcoholic fatty liver disease and the risk of clinical cardiovascular events: A systematic review and meta-analysis. Diabetology &amp; Metabolic Syndrome. 2017;11(1):209-216. doi: 10.1016/j.dsx.2016.12.033.</mixed-citation><mixed-citation xml:lang="en">Mahfood Haddad T., Hamdeh S., Kanmanthareddy A., et al. Nonalcoholic fatty liver disease and the risk of clinical cardiovascular events: A systematic review and meta-analysis. Diabetology &amp; Metabolic Syndrome. 2017;11(1):209-216. doi: 10.1016/j.dsx.2016.12.033.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO) EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. Journal of Hepatology. 2016(6):1388-1402. doi:10.1016/j.jhep.2015.11.004.</mixed-citation><mixed-citation xml:lang="en">European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO) EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. Journal of Hepatology. 2016(6):1388-1402. doi: 10.1016/j.jhep.2015.11.004.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Dyson J. K., Anstee Q. M., McPherson S. Liver Review Non-alcoholic fatty liver disease: a practical approach to treatment. Frontline Gastroenterology. 2014;5(4):277-286. doi: 10.1136/flgastro-2013-100404.</mixed-citation><mixed-citation xml:lang="en">Dyson J. K., Anstee Q. M., McPherson S. Liver Review Non-alcoholic fatty liver disease: a practical approach to treatment. Frontline Gastroenterology. 2014;5(4):277-286. doi: 10.1136/flgastro-2013-100404.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Sumida Y., Yoneda M. Current and future pharmacological therapies for NAFLD/NASH. Journal of Gastroenterology. 2018;53(3):362-376. doi: 10.1007/s00535-017-1415-1.</mixed-citation><mixed-citation xml:lang="en">Sumida Y., Yoneda M. Current and future pharmacological therapies for NAFLD/NASH. Journal of Gastroenterology. 2018;53(3):362-376. doi: 10.1007/s00535-017-1415-1.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Stefan N., Haring H. U., Cusi K. Non-alcoholic fattyliver disease: causes, diagnosis, cardiometabolic consequences, and treatment strategies. Lancet Diabetes Endocrinol. 2019(4):313-324. doi: 10.1016/S2213-8587(18)30154-2.</mixed-citation><mixed-citation xml:lang="en">Stefan N., Haring H. U., Cusi K. Non-alcoholic fattyliver disease: causes, diagnosis, cardiometabolic consequences, and treatment strategies. Lancet Diabetes Endocrinol. 2019(4):313-324. doi: 10.1016/S2213-8587(18)30154-2.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Бабенко А. Ю., Архипова А. Г., Байрашева В. К., Шляхто Е. В. Роль адипоцитокинов, грелина и инкретинов в предикции неалкогольной жировой болезни печени и ее лечении у пациентов с СД 2 типа. Экспериментальная и клиническая гастроэнтерология. 2018;150(2):121-136.</mixed-citation><mixed-citation xml:lang="en">Babenko A. Yu., Arkhipova A. G., Bayrasheva V. K., Shlyakhto E. V. Role of adipocytokines, ghrelin and incretins in predication of non-alcoholic fatty liver disease and its treatment in patients with type 2 diabetes. Experimental and Clinical Gastroenterology. 2018;150(2):121-136. (In Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Daisuke I., Satoshi S., Kazuyuki I., at al. Comparisonof Ipragliflozin and Pioglitazone Effects on Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes: A Randomized, 24-Week, Open Label, Active-Controlled Trial Diabetes Care. 2017;40:1364-1372. doi.org/10.2337/ dc17-0518.</mixed-citation><mixed-citation xml:lang="en">Daisuke I., Satoshi S., Kazuyuki I., at al. Comparisonof Ipragliflozin and Pioglitazone Effects on Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes: A Randomized, 24-Week, Open Label, Active-Controlled Trial Diabetes Care. 2017;40:1364-1372. doi.org/10.2337/ dc17-0518.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Armstrong M.J., Gaunt P., Aithal G. P., et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, doubleblind, randomised, placebo-controlled phase 2 study. Lancet. 2016;387(10019):679-690. doi: 10.1016/S0140-6736(15)00803-X.</mixed-citation><mixed-citation xml:lang="en">Armstrong M.J., Gaunt P., Aithal G. P., et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, doubleblind, randomised, placebo-controlled phase 2 study. Lancet. 2016;387(10019):679-690. doi: 10.1016/S0140-6736(15)00803-X.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Kuchay M. S., Krishan S., Mishra S. K., et al. Effect of empagliflozin on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease: a randomized controlled trial (E-LIFT Trial). Diabetes Care. 2018;41:1801-1808. doi:10.2337/dc18-0165.</mixed-citation><mixed-citation xml:lang="en">Kuchay M. S., Krishan S., Mishra S. K., et al. Effect of empagliflozin on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease: a randomized controlled trial (E-LIFT Trial). Diabetes Care. 2018;41:1801-1808. doi:10.2337/dc18-0165.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Bouchi R., Nakano Y., Fukuda T., et al. Reduction of visceral fat by liraglutide is associated with ameliorations of hepatic steatosis, albuminuria, and micro-inflammation in type 2 diabetic patients with insulin treatment: a randomized control trial. Endocrine Journal. 2017;64(3):269-281. doi: 10.1507/endocrj.EJ16-0449.</mixed-citation><mixed-citation xml:lang="en">Bouchi R., Nakano Y., Fukuda T., et al. Reduction of visceral fat by liraglutide is associated with ameliorations of hepatic steatosis, albuminuria, and micro-inflammation in type 2 diabetic patients with insulin treatment: a randomized control trial. Endocrine Journal. 2017;64(3):269-281. doi: 10.1507/endocrj.EJ16-0449.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Mells J.E., Fu P. P., Sharma S., et al. GLP-1 analog, li-raglutide, ameliorates hepatic steatosis and cardiac hypertrophy in C57BL/6J mice fed a Western diet. American journal of physiology. Gastrointestinal and liver physiology. 2012;302(2):225-235. doi:10.1152/ajp-gi.00274.2011.</mixed-citation><mixed-citation xml:lang="en">Mells J.E., Fu P. P., Sharma S., et al. GLP-1 analog, li-raglutide, ameliorates hepatic steatosis and cardiac hypertrophy in C57BL/6J mice fed a Western diet. American journal of physiology. Gastrointestinal and liver physiology. 2012;302(2):225-235. doi:10.1152/ajp-gi.00274.2011.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Zhou J. Y., Poudel A., Welchko R., et al. Liraglutide improves insulin sensitivity in high fat diet induced diabetic mice through multiple pathways. European Journal of Pharmacology. 2019;861: e172594. doi: 10.1016/j.ej-phar.2019.172594.</mixed-citation><mixed-citation xml:lang="en">Zhou J. Y., Poudel A., Welchko R., et al. Liraglutide improves insulin sensitivity in high fat diet induced diabetic mice through multiple pathways. European Journal of Pharmacology. 2019;861: e172594. doi: 10.1016/j.ej-phar.2019.172594.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Sharma S., Mells J. E., Fu P. P., Saxena N. K., Anania F. A. GLP-1 analogs reduce hepatocyte steatosis and improve survival by enhancing the unfolded protein response and promoting macroautophagy. PLOS One. 2011;6(9): e25269. doi: 10.1371/journal.pone.0025269.</mixed-citation><mixed-citation xml:lang="en">Sharma S., Mells J. E., Fu P. P., Saxena N. K., Anania F. A. GLP-1 analogs reduce hepatocyte steatosis and improve survival by enhancing the unfolded protein response and promoting macroautophagy. PLOS One. 2011;6(9): e25269. doi: 10.1371/journal.pone.0025269.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Moreira G. V., Azevedo F. F., Ribeiro L. M., et al. Liraglutide modulates gut microbiota and reduces NAFLD in obese mice. Th e Journal of Nutritional Biochemistry. 2018;62:143-154. doi: 10.1016/j.jnut-bio.2018.07.009.</mixed-citation><mixed-citation xml:lang="en">Moreira G. V., Azevedo F. F., Ribeiro L. M., et al. Liraglutide modulates gut microbiota and reduces NAFLD in obese mice. Th e Journal of Nutritional Biochemistry. 2018;62:143-154. doi: 10.1016/j.jnut-bio.2018.07.009.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Petit J. M., Cercueil J. P., Loffroy R., et al. Effect of liraglu-tide therapy on liver fat content in patients with inadequately controlled type 2 diabetes: the Lira-NAFLD study. Th e Journal of Clinical Endocrinology and Metabolism. 2017;102(2):407-415. doi:10.1210/jc.2016-2775.</mixed-citation><mixed-citation xml:lang="en">Petit J. M., Cercueil J. P., Loffroy R., et al. Effect of liraglu-tide therapy on liver fat content in patients with inadequately controlled type 2 diabetes: the Lira-NAFLD study. Th e Journal of Clinical Endocrinology and Metabolism. 2017;102(2):407-415. doi:10.1210/jc.2016-2775.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Armstrong M. J., Gaunt P., Aithal G. P., et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double blind, randomised, placebo-controlled phase 2 study. Lancet. 2016;387(10019):679-690. doi: 10.1016/s0140-6736(15)00803-x.</mixed-citation><mixed-citation xml:lang="en">Armstrong M. J., Gaunt P., Aithal G. P., et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double blind, randomised, placebo-controlled phase 2 study. Lancet. 2016;387(10019):679-690. doi: 10.1016/s0140-6736(15)00803-x.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Cusi K., Sattar N., Garda-Perez L.E., et al. Dulaglutide decreases plasma aminotransferases in people with type 2 diabetes in a pattern consistent with liver fat reduction: a post hoc analysis of the AWARD programme. Diabetic Medicine. 2018;35(10):1434-1439. doi: 10.1111/dme.13697.</mixed-citation><mixed-citation xml:lang="en">Cusi K., Sattar N., Garda-Perez L.E., et al. Dulaglutide decreases plasma aminotransferases in people with type 2 diabetes in a pattern consistent with liver fat reduction: a post hoc analysis of the AWARD programme. Diabetic Medicine. 2018;35(10):1434-1439. doi: 10.1111/dme.13697.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Kuchay, M.S., Krishan, S., Mishra, S.K., et al. Effect of dulaglutide on liver fat in patients with type 2 diabetes and NAFLD: randomised controlled trial (D-LIFT trial). Diabetologia. 2020;63(11):2434-2445. doi: 10.1007/s00125-020-05265-7.</mixed-citation><mixed-citation xml:lang="en">Kuchay, M.S., Krishan, S., Mishra, S.K., et al. Effect of dulaglutide on liver fat in patients with type 2 diabetes and NAFLD: randomised controlled trial (D-LIFT trial). Diabetologia. 2020;63(11):2434-2445. doi: 10.1007/s00125-020-05265-7.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Dufour J.-F., Caussy C., Loomba R. Combination therapy for non-alcoholic steatohepatitis: Rationale, opportunities and challenges. Gut. 2020;69:1877-1884. doi: 10.1136/gutjnl-2019-319104.</mixed-citation><mixed-citation xml:lang="en">Dufour J.-F., Caussy C., Loomba R. Combination therapy for non-alcoholic steatohepatitis: Rationale, opportunities and challenges. Gut. 2020;69:1877-1884. doi: 10.1136/gutjnl-2019-319104.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Angulo P., Hui J. M., Marchesini G., et al. NAFLD fibrosis score Online calculator. The NAFLD fibrosis score A noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45(4):846-854 doi:10.1002/hep.21496.</mixed-citation><mixed-citation xml:lang="en">Angulo P., Hui J. M., Marchesini G., et al. NAFLD fibrosis score Online calculator. The NAFLD fibrosis score A noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45(4):846-854 doi:10.1002/hep.21496.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Kristensen S.L., Rorth R., Jhund P. S., et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: A systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinology. 2019;7:776-785. doi: 10.1016/S2213-8587(19)30249-9.</mixed-citation><mixed-citation xml:lang="en">Kristensen S.L., Rorth R., Jhund P. S., et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: A systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinology. 2019;7:776-785. doi: 10.1016/S2213-8587(19)30249-9.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Mantovani A., Byrne C. D., Scorletti E., Mantzoros C. S., Targher G. Efficacy and safety of anti-hyperglycaemic drugs in patients with non-alcoholic fatty liver disease with or without diabetes: An updated systematic review of randomized controlled trials. Diabetes &amp; Metabolism. 2020;46(6):427-441. doi: 10.1016/j.diabet.2019.12.007.</mixed-citation><mixed-citation xml:lang="en">Mantovani A., Byrne C. D., Scorletti E., Mantzoros C. S., Targher G. Efficacy and safety of anti-hyperglycaemic drugs in patients with non-alcoholic fatty liver disease with or without diabetes: An updated systematic review of randomized controlled trials. Diabetes &amp; Metabolism. 2020;46(6):427-441. doi: 10.1016/j.diabet.2019.12.007.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Davies M.J., Bergenstal R., Bode B., et al. Efficacy of Liraglutide for Weight Loss Among Patients With Type 2 Diabetes: The SCALE Diabetes Randomized Clinical Trial. JAMA. 2015;314(7):687-699. doi: 10.1001/jama.2015.9676.</mixed-citation><mixed-citation xml:lang="en">Davies M.J., Bergenstal R., Bode B., et al. Efficacy of Liraglutide for Weight Loss Among Patients With Type 2 Diabetes: The SCALE Diabetes Randomized Clinical Trial. JAMA. 2015;314(7):687-699. doi: 10.1001/jama.2015.9676.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Frias J.P., Bonora E., Nevarez Ruiz L., et al. Efficacy and Safety of Dulaglutide 3.0 mg and 4.5 mg Versus Dulaglutide 1.5 mg in Metformin-Treated Patients With Type 2 Diabetes in a Randomized Controlled Trial (AWARD-11). Diabetes Care. 2021;44(3):765-773. doi: 10.2337/dc20-1473.</mixed-citation><mixed-citation xml:lang="en">Frias J.P., Bonora E., Nevarez Ruiz L., et al. Efficacy and Safety of Dulaglutide 3.0 mg and 4.5 mg Versus Dulaglutide 1.5 mg in Metformin-Treated Patients With Type 2 Diabetes in a Randomized Controlled Trial (AWARD-11). Diabetes Care. 2021;44(3):765-773. doi: 10.2337/dc20-1473.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Zhang L., Zhang M., Zhang Y., Tong N. Efficacy and safety of dulaglutide in patients with type 2 diabetes: a meta-analysis and systematic review. Scientific Reports. 2016;8(6):18904. doi: 10.1038/srep18904.</mixed-citation><mixed-citation xml:lang="en">Zhang L., Zhang M., Zhang Y., Tong N. Efficacy and safety of dulaglutide in patients with type 2 diabetes: a meta-analysis and systematic review. Scientific Reports. 2016;8(6):18904. doi: 10.1038/srep18904.</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Morieri M.L., Rigato M., Frison V., et al. Effectiveness of dulaglutide vs liraglutide and exenatide once-weekly. A real-world study and meta-analysis of observational studies. Metabolism. 2020;106:154190. doi:10.1016/j.metabol.2020.154190.</mixed-citation><mixed-citation xml:lang="en">Morieri M.L., Rigato M., Frison V., et al. Effectiveness of dulaglutide vs liraglutide and exenatide once-weekly. A real-world study and meta-analysis of observational studies. Metabolism. 2020;106:154190. doi: 10.1016/j.metabol.2020.154190.</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Tian F., Zheng Z., Zhang D., et al. Efficacy of liraglutide in treating type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease. Bioscience Reports. 2018;38(6): BSR20181304. doi: 10.1042/BSR20181304.</mixed-citation><mixed-citation xml:lang="en">Tian F., Zheng Z., Zhang D., et al. Efficacy of liraglutide in treating type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease. Bioscience Reports. 2018;38(6): BSR20181304. doi: 10.1042/BSR20181304.</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Armstrong M.J., Houlihan D. D., Rowe I. A., et al. Safety and efficacy of liraglutide in patients with type 2 diabetes and elevated liver enzymes: individual patient data meta-analysis of the LEAD program. Alimentary Pharmacology &amp; Therapeutics. 2013;37(2):234-242. doi: 10.1111/apt.12149.</mixed-citation><mixed-citation xml:lang="en">Armstrong M.J., Houlihan D. D., Rowe I. A., et al. Safety and efficacy of liraglutide in patients with type 2 diabetes and elevated liver enzymes: individual patient data meta-analysis of the LEAD program. Alimentary Pharmacology &amp; Therapeutics. 2013;37(2):234-242. doi: 10.1111/apt.12149.</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Lv X., Dong Y., Hu L., Lu F., Zhou C., Qin S. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for the management of nonalcoholic fatty liver disease (NAFLD): A systematic review. Endocrinology, Diabetes &amp; Metabolism Case Reports. 2020;3(3): e00163. doi: 10.1002/edm2.163.</mixed-citation><mixed-citation xml:lang="en">Lv X., Dong Y., Hu L., Lu F., Zhou C., Qin S. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for the management of nonalcoholic fatty liver disease (NAFLD): A systematic review. Endocrinology, Diabetes &amp; Metabolism Case Reports. 2020;3(3): e00163. doi: 10.1002/edm2.163.</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Teshome G., Ambachew S., Fasil A., Abebe M. Efficacy of Glucagon-Like Peptide-1 Analogs in Nonalcoholic Fatty Liver Disease: A Systematic Review. Hepatic medicine: evidence and research. 2020;12:139-151. doi:10.2147/HMER.S265631.</mixed-citation><mixed-citation xml:lang="en">Teshome G., Ambachew S., Fasil A., Abebe M. Efficacy of Glucagon-Like Peptide-1 Analogs in Nonalcoholic Fatty Liver Disease: A Systematic Review. Hepatic medicine: evidence and research. 2020;12:139-151. doi:10.2147/HMER.S265631.</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Promrat K., Kleiner D. E., Niemeier H. M., et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology. 2010 51: 21-29. doi: 10.1002/hep.23276.</mixed-citation><mixed-citation xml:lang="en">Promrat K., Kleiner D. E., Niemeier H. M., et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology. 2010 51: 21-29. doi: 10.1002/hep.23276.</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Bifari F., Manfrini R., Dei Cas M. et al. Multiple target tissue effects of GLP-1 analogues on non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Pharmacological Research. 2018;137:219-229. doi: 10.1016/j.phrs.2018.09.025.</mixed-citation><mixed-citation xml:lang="en">Bifari F., Manfrini R., Dei Cas M. et al. Multiple target tissue effects of GLP-1 analogues on non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Pharmacological Research. 2018;137:219-229. doi: 10.1016/j.phrs.2018.09.025.</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Liu J., Wang G., Jia Y., Xu Y. GLP-1 receptor agonists: effects on the progression of non-alcoholic fatty liver disease. Diabetes/Metabolism Research and Reviews 2015;31:329-335. doi: 10.1002/dmrr.2580.</mixed-citation><mixed-citation xml:lang="en">Liu J., Wang G., Jia Y., Xu Y. GLP-1 receptor agonists: effects on the progression of non-alcoholic fatty liver disease. Diabetes/Metabolism Research and Reviews 2015;31:329-335. doi: 10.1002/dmrr.2580.</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Li Z., Feng P. P., Zhao Z. B., et al. Liraglutide protects against inflammatory stress in non-alcoholic fatty liver by modulating Kupffer cells M2 polarization via cAMP-PKA-STAT3 signaling pathway. Biochemical and Biophysical Research Communications. 2019;510:20-6. doi: 10.1016/j.bbrc.2018.12.149.</mixed-citation><mixed-citation xml:lang="en">Li Z., Feng P. P., Zhao Z. B., et al. Liraglutide protects against inflammatory stress in non-alcoholic fatty liver by modulating Kupffer cells M2 polarization via cAMP-PKA-STAT3 signaling pathway. Biochemical and Biophysical Research Communications. 2019;510:20-6. doi: 10.1016/j.bbrc.2018.12.149.</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">Shiomi M., Tanaka Y., Takada T., Otori K. Determining whether the effect of liraglutide on non-alcoholic fatty liver disease depends on reductions in the body mass index. JGH Open. 2020;4(5):995-1001. doi: 10.1002/jgh3.12384.</mixed-citation><mixed-citation xml:lang="en">Shiomi M., Tanaka Y., Takada T., Otori K. Determining whether the effect of liraglutide on non-alcoholic fatty liver disease depends on reductions in the body mass index. JGH Open. 2020;4(5):995-1001. doi: 10.1002/jgh3.12384.</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>
