pmedpharmФармация и фармакологияPharmacy & Pharmacology2307-92662413-2241Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical Univer10.19163/2307-9266-2023-11-4-347-380pmedpharm-1386Research ArticleОБЗОРЫ, ЛЕКЦИИREVIEWS, LECTURESФизиология и фармакология рецептора глюкагоноподобного пептида-1Physiology and pharmacology of glucagon-like peptide-1 receptorhttps://orcid.org/0000-0002-1116-3425КуркинД. В.KurkinD. V.

доктор фармацевтических наук, доцент, директор Научно-образовательного института фармации им. К.М. Лакина, ФГБОУ ВО «Российский университет медицины» Минздрава России; профессор кафедры клинической фармакологии и интенсивной терапии, ФГБОУ ВО ВолгГМУ Минздрава России

127473, Россия, г. Москва, ул. Делегатская, д. 20/1.

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1.

Doctor of Sciences (Pharmacy), Asistant Professor, Head of the Scientific and Educational Institute of Pharmacy named after. K.M. Lakina of Russian University of Medicine; Professor of the Department of Clinical Pharmacology and Intensive Care of Volgograde State Medical University. 

Bld. 1, 20, Delegatskaya Str., Moscow, Russia, 127473.

1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131.

strannik986@mail.ruhttps://orcid.org/0000-0003-4694-3066БакулинД. А.BakulinD. A.

кандидат медицинских наук, руководитель Межкафедрального научно-образовательного центра фармации, Научно-образовательный институт фармации им. К.М. Лакина, ФГБОУ ВО «Российский университет медицины» Минздрава России.

127473, Россия, г. Москва, ул. Делегатская, д. 20/1

Candidate of Sciences (Medicine), Head of the Interdepartmental Scientific and Educational Center of Pharmacy of Scientific and Educational Institute of Pharmacy named after K.M. Lakin of Russian University of Medicine. 

Bld. 1, 20, Delegatskaya Str., Moscow, Russia, 127473

mbfdoc@gmail.comhttps://orcid.org/0000-0002-7119-3546МорковинЕ. И.MorkovinE. I.

кандидат медицинских наук, доцент, заведующий лабораторией нейропсихофармакологии НЦИЛС, ФГБОУ ВО ВолгГМУ Минздрава России.

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

Candidate of Sciences (Medicine), Assistant Professor, Head of the Laboratory of Neuropsychopharmacology of Volgograd State Medical University. 

1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

e.i.morkovin@gmail.comhttps://orcid.org/0000-0002-0258-4092ПетровВ. И.PetrovV. I.

доктор медицинских наук, профессор, академик РАН, заведующий кафедрой клинической фармакологии и интенсивной терапии, ФГБОУ ВО ВолгГМУ Минздрава России; главный внештатный специалист – клинический фармаколог Министерства здравоохранения РФ; заслуженный деятель науки РФ; заслуженный врач РФ. 

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

 

Doctor of Sciences (Medicine), Professor, Academician of RAS, Head of the Department of Clinical Pharmacology and Intensive Care of State Medical University; Chief Freelance Specialist, Clinical Pharmacologist of the Ministry of Healthcare of the Russian Federation, Honored Scientist of the Russian Federation, Honored Doctor of the Russian Federation. 

1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

brain@sprintnet.ruhttps://orcid.org/0000-0002-6997-1601СтрыгинА. В.StryginA. V.

кандидат медицинских наук, доцент, заместитель директора НЦИЛС, ФГБОУ ВО ВолгГМУ Минздрава России. 

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

Candidate of Sciences (Medicine), Assistant Professor, Deputy Director of Research Center for Innovative Medicines of Volgograd State Medical University. 

1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

drumsav@mail.ruhttps://orcid.org/0000-0003-1571-9301КоряноваК. Н.KoryanovaK. N.

кандидат фармацевтических наук, доцент кафедры фармакологии с курсом клинической фармакологии ПМФИ – филиала ФГБОУ ВО ВолгГМУ Минздрава России. 

357532, Россия, г. Пятигорск, пр-кт Калинина, д. 11

Candidate of Sciences (Pharmacy), Associate Professor of the Department of Pharmacology with a Course of Clinical Pharmacology, Pyatigorsk Medical and Pharmaceutical Institute – branch of Volgograd State Medical University.

11, Kalinin Ave., Pyatigorsk, Russia, 357532

kskor-16@mail.ruhttps://orcid.org/0000-0002-1116-3425ГорбуноваЮ. В.GorbunovaYu. V.

кандидат фармацевтических наук, заведующая лабораторией, Научно-образовательный институт фармации им. К.М. Лакина, ФГБОУ ВО «Российский университет медицины» Минздрава России.

127473, Россия, г. Москва, ул. Делегатская, д. 20/1

 

Candidate of Sciences (Medicine), Head of Laboratory of Scientific and Educational Institute of Pharmacy named after. K.M. Lakina of Russian University of Medicine.

Bld. 1, 20, Delegatskaya Str., Moscow, Russia, 127473

yvgorbunova@yandex.ruhttps://orcid.org/0000-0003-1506-2565КолосовЮ. А.KolosovYu. A.

кандидат медицинских наук, доцент, заместитель директора по учебной работе, Научно-образовательный институт фармации им. К.М. Лакина, ФГБОУ ВО «Российский университет медицины» Минздрава России.

127473, Россия, г. Москва, ул. Делегатская, д. 20/1

Candidate of Sciences (Medicine), Assistant Professor, Deputy Director for Academic Affairs of the Scientific and Educational Institute of Pharmacy named after. K.M. Lakina of Russian University of Medicine. 

Bld. 1, 20, Delegatskaya Str., Moscow, Russia, 127473

tronk79@gmail.comhttps://orcid.org/0000-0003-4333-322XИвановаО. В.IvanovaO. V.

кандидат фармацевтических наук, старший научный сотрудник, Научно-образовательный институт фармации им. К.М. Лакина, ФГБОУ ВО «Российский университет медицины» Минздрава России. 

127473, Россия, г. Москва, ул. Делегатская, д. 20/1

 

Candidate of Sciences (Pharmacy), Senior Researcher of the Scientific and Educational Institute of Pharmacy named after. K.M. Lakina of Russian University of Medicine. 

Bld. 1, 20, Delegatskaya Str., Moscow, Russia, 127473

ovivanova134@mail.ruhttps://orcid.org/0000-0003-0651-3205ПавловаЕ. В.PavlovaE. V.

младший научный сотрудник, Научно-образовательный институт фармации им. К.М. Лакина, ФГБОУ ВО «Российский университет медицины» Минздрава России. 

127473, Россия, г. Москва, ул. Делегатская, д. 20/1

junior researcher of the Scientific and Educational Institute of Pharmacy named after. K.M. Lakina of Russian University of Medicine. 

Bld. 1, 20, Delegatskaya Str., Moscow, Russia, 127473

lizapavlova1609@yandex.ruhttps://orcid.org/0000-0003-2673-6203ДжавахянМ. А.DzhavakhyanM. A.

доктор фармацевтических наук, доцент, заместитель директора по внедрению и разработке, Научно-образовательный институт фармации им. К.М. Лакина, ФГБОУ ВО «Российский университет медицины» Минздрава России.

127473, Россия, г. Москва, ул. Делегатская, д. 20/1

Doctor of Sciences (Pharmacy), Assistant Professor, Deputy Director for Implementation and Development of the Scientific and Educational Institute of Pharmacy named after. K.M. Lakina of Russian University of Medicine. 

Bld. 1, 20, Delegatskaya Str., Moscow, Russia, 127473

akopovamarina13@mail.ruhttps://orcid.org/0000-0002-7923-9916ЗаборовскийА. В.ZaborovskyA. V.

доктор медицинских наук, доцент, заведующий кафедрой фармакологии, ФГБОУ ВО «Российский университет медицины» Минздрава России. 

127473, Россия, г. Москва, ул. Делегатская, д. 20/1

Doctor of Sciences (Medicine), Assistant Professor, Head of the Department of Pharmacology of Russian University of Medicine. 

Bld. 1, 20, Delegatskaya Str., Moscow, Russia, 127473

azabor@mail.ruhttps://orcid.org/0000-0002-8445-1129СапароваВ. Б.SaparovaV. B.

научный сотрудник, Научно-образовательный институт фармации им. К.М. Лакина, ФГБОУ ВО «Российский университет медицины» Минздрава России. 

127473, Россия, г. Москва, ул. Делегатская, д. 20/1

 

researcher of the Scientific and Educational Institute of Pharmacy named after. K.M. Lakina of Russian University of Medicine. 

Bld. 1, 20, Delegatskaya Str., Moscow, Russia, 127473

Valeriya.Saparova@geropharm.comhttps://orcid.org/0000-0003-2308-0608МакаренкоИ. Е.MakarenkoI. E.

кандидат медицинских наук, научный сотрудник, Научно-образовательный институт фармации им. К.М. Лакина, ФГБОУ ВО «Российский университет медицины» Минздрава России; руководитель медицинского департамента, ЗАО «Фарм-Холдинг». 

127473, Россия, г. Москва, ул. Делегатская, д. 20/1.

198515, Россия, г. Санкт-Петербург, пос. Стрельна, ул. Связи, д. 34А

Candidate of Sciences (Medicine), – researcher of the Scientific and Educational Institute of Pharmacy named after. K.M. Lakina of Russian University of Medicine; Head of the Medical Department of Farm-Holding. 

Bld. 1, 20, Delegatskaya Str., Moscow, Russia, 127473.

34A, Svyaz Str., Strelna Vil., St. Petersburg, Russia, 198515.

Igor.Makarenko@geropharm.comhttps://orcid.org/0000-0003-4594-6097ДрайР. И.DraiR. I.

кандидат медицинских наук, директор ЗАО «Фарм-Холдинг». 

198515, Россия, г. Санкт-Петербург, пос. Стрельна, ул. Связи, д. 34А

Candidate of Sciences (Medicine), Director of Farm-Holding. 

34A, Svyaz Str., Strelna Vil., St. Petersburg, Russia, 198515

roman.drai@geropharm.comhttps://orcid.org/0000-0002-7756-3827ЧумаченкоА. Н.ChumachenkoA. N.

студент-исследователь, ФГБОУ ВО ВолгГМУ Минздрава России. 

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

 

student-researcher of Volgograd State Medical University. 

1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

nastya11386@icloud.comФедеральное государственное бюджетное образовательное учреждение высшего образования «Российский университет медицины» Министерства здравоохранения Российской Федерации. Федеральное государственное бюджетное образовательное учреждение высшего образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской Федерации.РоссияRussian University of Medicine. Volgograd State Medical University.Russian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Российский университет медицины» Министерства здравоохранения Российской ФедерацииРоссияRussian University of MedicineRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияVolgograd State Medical UniversityRussian FederationПятигорский медико-фармацевтический институт – филиал федерального государственного бюджетного образовательного учреждения высшего образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияPyatigorsk Medical and Pharmaceutical Institute – branch of Volgograd State Medical UniversityRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Российский университет медицины» Министерства здравоохранения Российской Федерации. Закрытое акционерное общество «Фарм-Холдинг»РоссияRussian University of Medicine. Closed joint-stock company “Farm-Holding”.Russian FederationЗакрытое акционерное общество «Фарм-Холдинг»РоссияClosed joint-stock company “Farm-Holding”.Russian Federation202309012024114347380Copyright © Куркин Д.В., Бакулин Д.А., Морковин Е.И., Петров В.И., Стрыгин А.В., Корянова К.Н., Горбунова Ю.В., Колосов Ю.А., Иванова О.В., Павлова Е.В., Джавахян М.А., Заборовский А.В., Сапарова В.Б., Макаренко И.Е., Драй Р.И., Чумаченко А.Н., 20242024Куркин Д.В., Бакулин Д.А., Морковин Е.И., Петров В.И., Стрыгин А.В., Корянова К.Н., Горбунова Ю.В., Колосов Ю.А., Иванова О.В., Павлова Е.В., Джавахян М.А., Заборовский А.В., Сапарова В.Б., Макаренко И.Е., Драй Р.И., Чумаченко А.Н.Kurkin D.V., Bakulin D.A., Morkovin E.I., Petrov V.I., Strygin A.V., Koryanova K.N., Gorbunova Y.V., Kolosov Y.A., Ivanova O.V., Pavlova E.V., Dzhavakhyan M.A., Zaborovsky A.V., Saparova V.B., Makarenko I.E., Drai R.I., Chumachenko A.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmpharm.ru/jour/article/view/1386

Современные подходы к лечению сахарного диабета 2 типа (СД2) направлены не только на контроль гликемии, но и на снижение кардиоваскулярных рисков. Рост распространенности заболевания и необходимость в эффективных вариантах лечения подчеркивают важность агонистов рецепторов глюкагоноподобного пептида-1 (ГПП-1) в структуре фармакотерапии.

Цель

Цель. Анализ литературы, касающейся физиологии ГПП-1, а также терапевтического потенциала и тенденций развития его агонистов.

Материалы и методы

Материалы и методы. Поиск материала для написания обзора проводили с использованием реферативных баз PubMed, Google Scholar и e-Library. Поиск осуществляли по публикациям в период с 2000 по 2023 годы, с использованием следующих ключевых слов: «ГПП-1»; «агонисты ГПП-1Р»; «ГИП»; «эксенатид»; «лираглутид»; «дулаглутид»; «семаглутид»; «ликсисенатид»; «албиглутид»; «таспоглутид» с учетом различных вариантов их написания.

Результаты

Результаты. Взаимодействие практически всех компонентов пищи с энтероэндокринными клетками кишечника приводит к секреции в кровь инкретинов (прежде всего ГПП-1), запускающих комплекс физиологических реакций, направленных, в первую очередь, на быструю утилизацию поступающей глюкозы (регуляция секреции инсулина и глюкагона), а также центральную регуляцию пищевого поведения (замедление опорожнения желудка и формирование чувства насыщения). Широкое распространение рецептора к ГПП-1 в различных тканях и органах, его связь с внутриклеточными сигнальными каскадами, направленными на запуск энергозатратных процессов ремоделирования (восстановления) в клетках эндотелия, сердца, нейронах, бета-клетках и др., является основой для широкого спектра плейотропных эффектов ГПП-1, не связанных с его гипогликемическим действием. Открытие синтетических агонистов рецепторов ГПП-1 с длительным периодом действия дало возможность не только терапевтически воздействовать на различные звенья нарушений углеводного обмена, но и увеличить функциональные резервы органов-мишеней СД, снижая риск развития осложнений заболевания. Инкретиноподобные препараты хорошо переносятся, самым распространенным побочным эффектом является тошнота. Факторы, ограничивающие более широкое использование препаратов, включают высокую стоимость и преимущественную форму – раствор для подкожного введения. Текущие исследования связаны с разработкой препаратов с пролонгированным действием, пероральной формы, двойных и тройных агонистов, фиксированных комбинаций, а также препаратов малых молекул.

Заключение

Заключение. Агонисты рецепторов ГПП-1 представляют собой класс эффективных и безопасных лекарственных средств для терапии СД и ожирения, который стремительно развивается по самым передовым направлениям фармации. Дальнейшее развитие этой группы и решение обозначенных задач откроет новые возможности для лечения СД и его осложнений.

Modern approaches to the treatment of type 2 diabetes mellitus (T2DM) are aimed not only at glycemic control, but also at reducing cardiovascular risks. The increasing prevalence of the disease and the need for effective treatment options highlight the importance of glucagon-like peptide-1 (GLP-1) receptor agonists in the pharmacotherapy structure.

The aim of the work was to review the literature regarding the physiology of GLP-1 and the therapeutic potential and development trends of its agonists.

Materials and methods

Materials and methods. The search for the review materials was carried out using the abstract databases of PubMed, Google Scholar and e-Library. The search was carried out for publications from 2000 to 2023, using the following keywords: “GLP-1”; “GLP-1R agonists”; “GIP”; “exenatide”; “liraglutide”; “dulaglutide”; “semaglutide”; “lixisenatide”; “albiglutide”; “taspoglutide” taking into account various spellings.

Results

Results. The interaction of almost all food components with enteroendocrine cells of the intestine leads to the secretion of incretins (primarily GLP-1) into the blood, triggering a complex of physiological reactions aimed primarily at the rapid utilization of incoming glucose (regulation of insulin and glucagon secretion), as well as the central regulation of dietary behavior (slowing gastric emptying and the formation of a feeling of satiety). A wide distribution of the GLP-1 receptor in various tissues and organs, its connection with intracellular signaling cascades aimed at launching energy-consuming remodeling (recovery) processes in endothelial cells, heart, neurons, beta cells, etc., is the basis for a wide range of pleiotropic effects of GLP-1 unrelated to its hypoglycemic effect. The discovery of synthetic GLP-1 receptor agonists with a long period of action has made it possible not only to therapeutically influence various parts of carbohydrate metabolism disorders, but also to increase the functional reserves of the target diabetes organs, reducing the risk of developing complications of the disease. Incretin-like drugs are well tolerated, with nausea being the most common side effect. The factors limiting a wider use of the drugs include their high cost and the preferred form of a subcutaneous solution. The current research is focused on the development of long-acting, oral, dual and triple agonists, fixed-dose combinations, and small molecule drugs.

Conclusion

Conclusion. GLP-1 receptor agonists are a class of effective and safe drugs for the treatment of diabetes and obesity, which is rapidly developing in the most advanced areas of pharmacy. A further development of this group and the solution of the identified problems will open up new opportunities for the treatment of diabetes and its complications.

ГПП-1агонисты глюкагоноподобного рецептора-1сахарный диабетинкретиныGLP-1glucagon-like receptor-1 agonistsdiabetes mellitusincretinsРабота выполнена в рамках гранта РНФ (проект № 20-75-10013).The work was carried out within the framework of a grant from the Russian Science Foundation(Project No. 20-75-10013).ReferencesДедов И.И., Шестакова М.В., Майоров А.Ю., Мокрышева Н.Г., Викулова О.К., Галстян Г.Р., Кураева Т.Л., Петеркова В.А., Смирнова О.М., Старостина Е.Г., Суркова Е.В., Сухарева О.Ю., Токмакова А.Ю., Шамхалова М.Ш., Ярек-Мартынова И.Я., Артемова Е.В., Бешлиева Д.Д., Бондаренко О.Н., Волеводз Н.Н., Гомова И.С., Григорян О.Р., Джемилова З.Н., Есаян Р.М., Ибрагимова Л.И., Калашников В.Ю., Кононенко И.В., Лаптев Д.Н., Липатов Д.В., Мельникова О.Г., Михина М.С., Мичурова М.С., Мотовилин О.Г., Никонова Т.В., Роживанов Р.В., Скляник И.А., Шестакова Е.А. «Алгоритмы специализированной медицинской помощи больным сахарным диабетом». Под редакцией И.И. Дедова, М.В. Шестаковой, А.Ю. Майорова. 10-й выпуск // Сахарный диабет. – 2021. – Т. 24, № 1S. – С. 1–148. DOI: 10.14341/DM12802Dedov II, Shestakova MV, Mayorov AYu, Mokrysheva NG, Vikulova OK, Galstyan GR, Kuraeva TL, Peterkova VA, Smirnova OM, Starostina EG, Surkova EV, Sukhareva OY, Tokmakova AY, Shamkhalova MS, Jarek-Martynova IR, Artemova EV, Beshlieva DD, Bondarenko ON, Volevodz NN, Gomova IS, Grigoryan OR, Dzhemilova ZN, Esayan RM, Ibragimova LI, Kalashnikov VY, Kononenko IV, Laptev DN, Lipatov DV, Melnikova OG, Mikhina MS, Michurova MS, Motovilin OG, Nikonova TV, Rozhivanov RV, Sklyanik IA, Shestakova EA Standards of specialized diabetes care Edited by Dedov II, Shestakova MV, Mayorov AYu 10th edition. Diabetes mellitus. 2021;24(1S):1–148. DOI: 10.14341/DM12802. RussianBlonde L., Umpierrez G.E., Reddy S.S., McGill J.B., Berga S.L., Bush M., Chandrasekaran S., DeFronzo R.A., Einhorn D., Galindo R.J., Gardner T.W., Garg R., Garvey W.T., Hirsch I.B., Hurley D.L., Izuora K., Kosiborod M., Olson D., Patel S.B., Pop-Busui R., Sadhu A.R., Samson S.L., Stec C., Tamborlane W.V. Jr, Tuttle K.R., Twining C., Vella A., Vellanki P., Weber S.L. American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update // Endocr Pract. – 2022. – Vol. 28, No. 10. – P. 923–1049. DOI: 10.1016/j.eprac.2022.08.002Blonde L, Umpierrez GE, Reddy SS, McGill JB, Berga SL, Bush M, Chandrasekaran S, DeFronzo RA, Einhorn D, Galindo RJ, Gardner TW, Garg R, Garvey WT, Hirsch IB, Hurley DL, Izuora K, Kosiborod M, Olson D, Patel SB, Pop-Busui R, Sadhu AR, Samson SL, Stec C, Tamborlane WV Jr, Tuttle KR, Twining C, Vella A, Vellanki P, Weber SL. American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. Endocr Pract. 2022;28(10):923–1049. DOI: 10.1016/j.eprac.2022.08.002Saisho Y. Incretin-based therapy and pancreatitis: accumulating evidence and unresolved questions // Ann Transl Med. – 2018. – Vol. 6, No. 7. – P. 131. DOI: 10.21037/atm.2018.02.24Saisho Y. Incretin-based therapy and pancreatitis: accumulating evidence and unresolved questions. Ann Transl Med. 2018;6(7):131. DOI: 10.21037/atm.2018.02.24Müller T.D., Finan B., Bloom S.R., D’Alessio D., Drucker D.J., Flatt P.R., Fritsche A., Gribble F., Grill H.J., Habener J.F., Holst J.J., Langhans W., Meier J.J., Nauck M.A., Perez-Tilve D., Pocai A., Reimann F., Sandoval D.A., Schwartz T.W., Seeley R.J., Stemmer K., Tang-Christensen M., Woods S.C., DiMarchi R.D., Tschöp M.H. Glucagon-like peptide 1 (GLP-1) // Mol Metab. – 2019. – Vol. 30. – P. 72–130. DOI: 10.1016/j.molmet.2019.09.010Müller TD, Finan B, Bloom SR, D’Alessio D, Drucker DJ, Flatt PR, Fritsche A, Gribble F, Grill HJ, Habener JF, Holst JJ, Langhans W, Meier JJ, Nauck MA, Perez-Tilve D, Pocai A, Reimann F, Sandoval DA, Schwartz TW, Seeley RJ, Stemmer K, Tang-Christensen M, Woods SC, DiMarchi RD, Tschöp MH. Glucagon-like peptide 1 (GLP-1). Mol Metab. 2019;30:72–130. DOI: 10.1016/j.molmet.2019.09.010Holst J.J. From the Incretin Concept and the Discovery of GLP-1 to Today’s Diabetes Therapy // Front Endocrinol (Lausanne). – 2019. – Vol. 10. – P. 260. DOI: 10.3389/fendo.2019.00260Holst JJ. From the incretin concept and the discovery of GLP-1 to today’s diabetes therapy. Front Endocrinol (Lausanne). 2019;10:260. DOI: 10.3389/fendo.2019.00260Sharma D., Verma S., Vaidya S., Kalia K., Tiwari V. Recent updates on GLP-1 agonists: Current advancements & challenges // Biomed. Pharmacother. – 2018. – Vol. 108. – P. 952–962. DOI: 10.1016/j.biopha.2018.08.088Sharma D, Verma S, Vaidya S, Kalia K, Tiwari V. Recent updates on GLP-1 agonists: Current advancements & challenges. Biomed. Pharmacother. 2018;108:952–62. DOI: 10.1016/j.biopha.2018.08.088Brierley D.I., de Lartigue G. Reappraising the role of the vagus nerve in GLP-1-mediated regulation of eating // Br J Pharmacol. – 2022. – Vol. 179, No. 4. – P. 584–599. DOI: 10.1111/bph.15603Brierley DI, de Lartigue G. Reappraising the role of the vagus nerve in GLP-1-mediated regulation of eating. Br J Pharmacol. 2022;179(4):584–99. DOI: 10.1111/bph.15603Singh I., Wang L., Xia B., Liu J., Tahiri A., El Ouaamari A., Wheeler M.B., Pang Z.P. Activation of arcuate nucleus glucagon-like peptide-1 receptor-expressing neurons suppresses food intake // Cell Biosci. – 2022. – Vol. 12, No. 1. – P. 178. DOI: 10.1186/s13578-022-00914-3Singh I, Wang L, Xia B, Liu J, Tahiri A, El Ouaamari A, Wheeler MB, Pang ZP. Activation of arcuate nucleus glucagon-like peptide-1 receptor-expressing neurons suppresses food intake. Cell Biosci. 2022;12(1):178. DOI: 10.1186/s13578-022-00914-3Gabe M.B.N., Skov-Jeppesen K., Gasbjerg L.S., Schiellerup S.P., Martinussen C., Gadgaard S., Boer G.A., Oeke J., Torz L.J., Veedfald S., Svane M.S., Bojsen-Møller K.N., Madsbad S., Holst J.J., Hartmann B., Rosenkilde M.M. GIP and GLP-2 together improve bone turnover in humans supporting GIPR-GLP-2R co-agonists as future osteoporosis treatment // Pharmacol Res. – 2022. – Vol. 176. – P. 106058. DOI: 10.1016/j.phrs.2022.106058Gabe MBN, Skov-Jeppesen K, Gasbjerg LS, Schiellerup SP, Martinussen C, Gadgaard S, Boer GA, Oeke J, Torz LJ, Veedfald S, Svane MS, Bojsen-Møller KN, Madsbad S, Holst JJ, Hartmann B, Rosenkilde MM. GIP and GLP-2 together improve bone turnover in humans supporting GIPR-GLP-2R co-agonists as future osteoporosis treatment. Pharmacol Res. 2022;176:106058. DOI: 10.1016/j.phrs.2022.106058Henriksen D.B., Alexandersen P., Hartmann B., Adrian C.L., Byrjalsen I., Bone H.G., Holst J.J., Christiansen C. Four-month treatment with GLP-2 significantly increases hip BMD: a randomized, placebo-controlled, dose-ranging study in postmenopausal women with low BMD // Bone. – 2009. – Vol. 45, No. 5. – P. 833–842. DOI: 10.1016/j.bone.2009.07.008Henriksen DB, Alexandersen P, Hartmann B, Adrian CL, Byrjalsen I, Bone HG, Holst JJ, Christiansen C. Four-month treatment with GLP-2 significantly increases hip BMD: a randomized, placebo-controlled, dose-ranging study in postmenopausal women with low BMD. Bone. 2009;45(5):833–42. DOI: 10.1016/j.bone.2009.07.008Greco E.V., Russo G., Giandalia A., Viazzi F., Pontremoli R., De Cosmo S. GLP-1 Receptor Agonists and Kidney Protection // Medicina (Kaunas). – 2019. – Vol. 55, No. 6. – P. 233. DOI: 10.3390/medicina55060233Greco EV, Russo G, Giandalia A, Viazzi F, Pontremoli R, De Cosmo S. GLP-1 receptor agonists and kidney protection. Medicina (Kaunas). 2019;55(6):233. DOI: 10.3390/medicina55060233Zhao X., Wang M., Wen Z., Lu Z., Cui L., Fu C., Xue H., Liu Y., Zhang Y. GLP-1 Receptor Agonists: Beyond Their Pancreatic Effects // Front. Endocrinol. (Lausanne). – 2021. – Vol. 12. – P. 721135. DOI: 10.3389/fendo.2021.721135Zhao X, Wang M, Wen Z, Lu Z, Cui L, Fu C, Xue H, Liu Y, Zhang Y. GLP-1 receptor agonists: beyond their pancreatic effects. front. Endocrinol. (Lausanne). 2021;12:721135. DOI: 10.3389/fendo.2021.721135Whalley N.M., Pritchard L.E., Smith D.M., White A. Processing of proglucagon to GLP-1 in pancreatic α-cells: is this a paracrine mechanism enabling GLP-1 to act on β-cells? // J Endocrinol. – 2011. – Vol. 211, No. 1. – P. 99–106. DOI: 10.1530/JOE-11-0094Whalley NM, Pritchard LE, Smith DM, White A. Processing of proglucagon to GLP-1 in pancreatic α-cells: is this a paracrine mechanism enabling GLP-1 to act on β-cells? J Endocrinol. 2011;211(1):99–106. DOI: 10.1530/JOE-11-0094Wideman R.D., Yu I.L., Webber T.D., Verchere C.B., Johnson J.D., Cheung A.T., Kieffer T.J. Improving function and survival of pancreatic islets by endogenous production of glucagon-like peptide 1 (GLP-1) // Proc Natl Acad Sci USA. – 2006. – Vol. 103, No. 36. – P. 13468–13473. DOI: 10.1073/pnas.0600655103Wideman RD, Yu IL, Webber TD, Verchere CB, Johnson JD, Cheung AT, Kieffer TJ. Improving function and survival of pancreatic islets by endogenous production of glucagon-like peptide 1 (GLP-1). Proc Natl Acad Sci USA. 2006;103(36):13468–73. DOI: 10.1073/pnas.0600655103Jun L.S., Millican R.L., Hawkins E.D., Konkol D.L., Showalter A.D., Christe M.E., Michael M.D., Sloop K.W. Absence of glucagon and insulin action reveals a role for the GLP-1 receptor in endogenous glucose production // Diabetes. – 2015. – Vol. 64, No. 3. – P. 819–827. DOI: 10.2337/db14-1052Jun LS, Millican RL, Hawkins ED, Konkol DL, Showalter AD, Christe ME, Michael MD, Sloop KW. Absence of glucagon and insulin action reveals a role for the GLP-1 receptor in endogenous glucose production. Diabetes. 2015;64(3):819–27. DOI: 10.2337/db14-1052Capozzi M.E., Svendsen B., Encisco S.E., Lewandowski S.L., Martin M.D., Lin H., Jaffe J.L., Coch R.W., Haldeman J.M., MacDonald P.E., Merrins M.J., D’Alessio D.A., Campbell J.E. β Cell tone is defined by proglucagon peptides through cAMP signaling // JCI Insight. – 2019. – Vol. 4, No. 5. – P. e126742. DOI: 10.1172/jci.insight.126742Capozzi ME, Svendsen B, Encisco SE, Lewandowski SL, Martin MD, Lin H, Jaffe JL, Coch RW, Haldeman JM, MacDonald PE, Merrins MJ, D’Alessio DA, Campbell JE. β Cell tone is defined by proglucagon peptides through cAMP signaling. JCI Insight. 2019;4(5):e126742. DOI: 10.1172/jci.insight.126742Zhao F., Zhou Q., Cong Z., Hang K., Zou X., Zhang C., Chen Y., Dai A., Liang A., Ming Q., Wang M., Chen L.N., Xu P., Chang R., Feng W., Xia T., Zhang Y., Wu B., Yang D., Zhao L., Xu H.E., Wang M.W. Structural insights into multiplexed pharmacological actions of tirzepatide and peptide 20 at the GIP, GLP-1 or glucagon receptors // Nat Commun. – 2022. – Vol. 13, No. 1. – P. 1057. DOI: 10.1038/s41467-022-28683-0Zhao F, Zhou Q, Cong Z, Hang K, Zou X, Zhang C, Chen Y, Dai A, Liang A, Ming Q, Wang M, Chen LN, Xu P, Chang R, Feng W, Xia T, Zhang Y, Wu B, Yang D, Zhao L, Xu HE, Wang MW. Structural insights into multiplexed pharmacological actions of tirzepatide and peptide 20 at the GIP, GLP-1 or glucagon receptors. Nat Commun. 2022;13(1):1057. DOI: 10.1038/s41467-022-28683-0Svendsen B., Larsen O., Gabe M.B.N., Christiansen C.B., Rosenkilde M.M., Drucker D.J., Holst J.J. Insulin Secretion Depends on Intra-islet Glucagon Signaling // Cell Rep. – 2018. – Vol. 25, No. 5. – P. 1127–1134.e2. DOI: 10.1016/j.celrep.2018.10.018Svendsen B, Larsen O, Gabe MBN, Christiansen CB, Rosenkilde MM, Drucker DJ, Holst JJ. Insulin Secretion Depends on Intra-islet Glucagon Signaling. Cell Rep. 2018;25(5):1127–1134.e2. DOI: 10.1016/j.celrep.2018.10.018Holst J.J. Glucagon-like peptide-1: Are its roles as endogenous hormone and therapeutic wizard congruent? // J Intern Med. – 2022. – Vol. 291, No. 5. – P. 557–573. DOI: 10.1111/joim.13433Holst J.J. Glucagon-like peptide-1: Are its roles as endogenous hormone and therapeutic wizard congruent? J Intern Med. – 2022;291(5):557–573. DOI: 10.1111/joim.13433Malik F., Li Z. Non-peptide agonists and positive allosteric modulators of glucagon-like peptide-1 receptors: Alternative approaches for treatment of Type 2 diabetes // Br J Pharmacol. – 2022. – Vol. 179, No. 4. – P. 511–525. DOI: 10.1111/bph.15446Malik F, Li Z. Non-peptide agonists and positive allosteric modulators of glucagon-like peptide-1 receptors: Alternative approaches for treatment of Type 2 diabetes. Br J Pharmacol. 2022;179(4):511–25. DOI: 10.1111/bph.15446McLean B.A., Wong C.K., Campbell J.E., Hodson D.J., Trapp S., Drucker D.J. Revisiting the Complexity of GLP-1 Action from Sites of Synthesis to Receptor Activation // Endocr Rev. – 2021. – Vol. 42, No. 2. – P. 101–132. DOI: 10.1210/endrev/bnaa032McLean BA, Wong CK, Campbell JE, Hodson DJ, Trapp S, Drucker DJ. Revisiting the complexity of GLP-1 action from sites of synthesis to receptor activation. Endocr Rev. 2021;42(2):101–132. DOI: 10.1210/endrev/bnaa032Choe H.J., Cho Y.M. Peptidyl and Non-Peptidyl Oral Glucagon-Like Peptide-1 Receptor Agonists // Endocrinol. Metab. (Seoul). – 2021. – Vol. 36, No. 1. – P. 22–29. DOI: 10.3803/EnM.2021.102Choe HJ., Cho YM. Peptidyl and Non-Peptidyl Oral Glucagon-Like Peptide-1 Receptor Agonists. Endocrinol. Metab. (Seoul). 2021;36(1):22–9. DOI: 10.3803/EnM.2021.102Kawai T., Sun B., Yoshino H., Feng D., Suzuki Y., Fukazawa M., Nagao S., Wainscott D.B., Showalter A.D., Droz B.A., Kobilka T.S., Coghlan M.P., Willard F.S., Kawabe Y., Kobilka B.K., Sloop K.W. Structural basis for GLP-1 receptor activation by LY3502970, an orally active nonpeptide agonist // Proc. Natl. Acad. Sci. USA. – 2020. – Vol. 117, No. 47. – P. 29959–29967. DOI: 10.1073/pnas.2014879117Kawai T, Sun B, Yoshino H, Feng D, Suzuki Y, Fukazawa M, Nagao S, Wainscott DB, Showalter AD, Droz BA, Kobilka TS, Coghlan MP, Willard FS, Kawabe Y, Kobilka BK, Sloop KW. Structural basis for GLP-1 receptor activation by LY3502970, an orally active nonpeptide agonist. Proc Natl Acad Sci USA. 2020;117(47):29959–67. DOI: 10.1073/pnas.2014879117Pyke C., Heller R.S., Kirk R.K., Ørskov C., Reedtz-Runge S., Kaastrup P., Hvelplund A., Bardram L., Calatayud D., Knudsen L.B. GLP-1 receptor localization in monkey and human tissue: novel distribution revealed with extensively validated monoclonal antibody // Endocrinology. – 2014. – Vol. 155, No. 4. – P. 1280–1290. DOI: 10.1210/en.2013-1934Pyke C, Heller RS, Kirk RK, Ørskov C, Reedtz-Runge S, Kaastrup P, Hvelplund A, Bardram L, Calatayud D, Knudsen LB. GLP-1 receptor localization in monkey and human tissue: novel distribution revealed with extensively validated monoclonal antibody. Endocrinology. 2014;155(4):1280–90. DOI: 10.1210/en.2013-1934Richards P., Parker H.E., Adriaenssens A.E., Hodgson J.M., Cork S.C., Trapp S., Gribble F.M., Reimann F. Identification and characterization of GLP-1 receptor-expressing cells using a new transgenic mouse model // Diabetes. – 2014. – Vol. 63, No. 4. – P. 1224–1233. DOI: 10.2337/db13-1440Richards P, Parker HE, Adriaenssens AE, Hodgson JM, Cork SC, Trapp S, Gribble FM, Reimann F. Identification and characterization of GLP-1 receptor-expressing cells using a new transgenic mouse model. Diabetes. 2014;63(4):1224–33. DOI: 10.2337/db13-1440Hjørne A.P., Modvig I.M., Holst J.J. The Sensory Mechanisms of Nutrient-Induced GLP-1 Secretion // Metabolites. – 2022. – Vol. 12, No. 5. – P. 420. DOI: 10.3390/metabo12050420Hjørne AP, Modvig IM, Holst JJ. The sensory mechanisms of nutrient-induced GLP-1 secretion. Metabolites. – 2022;12(5):420. DOI: 10.3390/metabo12050420Mayendraraj A., Rosenkilde M.M., Gasbjerg L.S. GLP-1 and GIP receptor signaling in beta cells – а review of receptor interactions and co-stimulation // Peptides. – 2022. – Vol. 151. – P. 170749. DOI: 10.1016/j.peptides.2022.170749Mayendraraj A, Rosenkilde MM, Gasbjerg LS. GLP-1 and GIP receptor signaling in beta cells – A review of receptor interactions and co-stimulation. Peptides. 2022;151:170749. DOI: 10.1016/j.peptides.2022.170749Wootten D., Reynolds C.A., Smith K.J., Mobarec J.C., Koole C., Savage E.E., Pabreja K., Simms J., Sridhar R., Furness S.G.B., Liu M., Thompson P.E., Miller L.J., Christopoulos A., Sexton P.M. The Extracellular Surface of the GLP-1 Receptor Is a Molecular Trigger for Biased Agonism // Cell. – 2016. – Vol. 165, No. 7. – P. 1632–1643. DOI: 10.1016/j.cell.2016.05.023Wootten D, Reynolds CA, Smith KJ, Mobarec JC, Koole C, Savage EE, Pabreja K, Simms J, Sridhar R, Furness SGB, Liu M, Thompson PE, Miller LJ, Christopoulos A, Sexton PM. The extracellular surface of the GLP-1 receptor is a molecular trigger for biased agonism. Cell. 2016;165(7):1632–43. DOI: 10.1016/j.cell.2016.05.023Spreckley E., Murphy K.G. The L-Cell in Nutritional Sensing and the Regulation of Appetite // Front Nutr. – 2015. – Vol. 2. – P. 23. DOI: 10.3389/fnut.2015.00023Spreckley E, Murphy KG. The L-cell in nutritional sensing and the regulation of appetite. Front Nutr. 2015;2:23. DOI: 10.3389/fnut.2015.00023Wang X., Liu H., Chen J., Li Y., Qu S. Multiple Factors Related to the Secretion of Glucagon-Like Peptide-1 // Int J Endocrinol. – 2015. – Vol. 2015. – P. 651757. DOI: 10.1155/2015/651757Wang X, Liu H, Chen J, Li Y, Qu S. Multiple factors related to the secretion of glucagon-like peptide-1. Int J Endocrinol. 2015;2015:651757. DOI: 10.1155/2015/651757Alavi S.E., Cabot P.J., Moyle P.M. Glucagon-Like Peptide-1 Receptor Agonists and Strategies To Improve Their Efficiency // Mol Pharm. – 2019. – Vol. 16, No. 6. – P. 2278–2295. DOI: 10.1021/acs.molpharmaceut.9b00308Alavi SE, Cabot PJ, Moyle PM. Glucagon-Like Peptide-1 Receptor Agonists and Strategies To Improve Their Efficiency. Mol Pharm. 2019;16(6):2278–95. DOI: 10.1021/acs.molpharmaceut.9b00308Eriksson L., Nyström T. Antidiabetic agents and endothelial dysfunction – beyond glucose control. Basic Clin Pharmacol Toxicol. – 2015. – Vol. 117, No. 1. – P. 15–25. DOI: 10.1111/bcpt.12402Eriksson L, Nyström T. Antidiabetic agents and endothelial dysfunction – beyond glucose control. Basic Clin Pharmacol Toxicol. 2015;117(1):15–25. DOI: 10.1111/bcpt.12402Calanna S., Christensen M., Holst J.J., Laferrère B., Gluud L.L., Vilsbøll T., Knop F.K. Secretion of glucagon-like peptide-1 in patients with type 2 diabetes mellitus: systematic review and meta-analyses of clinical studies // Diabetologia. – 2013. – Vol. 56, No. 5. – P. 965–972. DOI: 10.1007/s00125-013-2841-0Calanna S, Christensen M, Holst JJ, Laferrère B, Gluud LL, Vilsbøll T, Knop FK. Secretion of glucagon-like peptide-1 in patients with type 2 diabetes mellitus: systematic review and meta-analyses of clinical studies. Diabetologia. 2013;56(5):965–72. DOI: 10.1007/s00125-013-2841-0Kuhre R.E., Frost C.R., Svendsen B., Holst J.J. Molecular mechanisms of glucose-stimulated GLP-1 secretion from perfused rat small intestine // Diabetes. – 2015. – Vol. 64, No. 2. – P. 370–382. DOI: 10.2337/db14-0807Kuhre RE, Frost CR, Svendsen B, Holst JJ. Molecular mechanisms of glucose-stimulated GLP-1 secretion from perfused rat small intestine. Diabetes. 2015;64(2):370–82. DOI: 10.2337/db14-0807Tyurenkov I.N., Ozerov A.A., Kurkin D.V., Logvinova E.O., Bakulin D.A., Volotova E.V., Borodin D.D. Structure and biological activity of endogenous and synthetic agonists of GPR119 // Russian Chemical Reviews. – 2018. – Vol. 87, No. 2. – P. 151–166. DOI: 10.1070/rcr4737Tyurenkov IN, Ozerov AA, Kurkin DV, Logvinova EO, Bakulin DA, Volotova EV, Borodin DD. Structure and biological activity of endogenous and synthetic agonists of GPR119. Russian Chemical Reviews. 2018;87(2):151–66. DOI: 10.1070/rcr4737Тюренков И.Н., Куркин Д.В., Волотова Е.В., Бакулин Д.А. Роль микрофлоры кишечника, состава пищи, GPR41- и GPR43-рецепторов к короткоцепочечным жирным кислотам в энергетическом обмене позвоночных животных // Успехи физиологических наук. – 2017. – Т. 48, № 2. – С. 100–112.Tyurenkov IN, Kurkin DV, Volotova EV, Bakulin DA. The role of intestinal microflora, food composition, GPR41- and GPR43-receptors for short chain fatty acids in energy metabolism of vertebrates. Uspekhi fiziologicheskih nauk. 2017;48(2):100–12. RussianTyurenkov I.N., Kurkin D.V., Bakulin D.A., Volotova E.V., Morkovin E.I., Chafeev M.A., Karapetian R.N. Chemistry and Hypoglycemic Activity of GPR119 Agonist ZB-16 // Front Endocrinol (Lausanne). – 2018. – Vol. 9. – P. 543. DOI: 10.3389/fendo.2018.00543Tyurenkov IN, Kurkin DV, Bakulin DA, Volotova EV, Morkovin EI, Chafeev MA, Karapetian RN. Chemistry and Hypoglycemic Activity of GPR119 Agonist ZB-16. Front Endocrinol (Lausanne). 2018;9:543. DOI: 10.3389/fendo.2018.00543Im D.S. GPR119 and GPR55 as Receptors for Fatty Acid Ethanolamides, Oleoylethanolamide and Palmitoylethanolamide // Int J Mol Sci. – 2021. – Vol. 22, No. 3. – P. 1034. DOI: 10.3390/ijms22031034Im DS. GPR119 and GPR55 as receptors for fatty acid ethanolamides, oleoylethanolamide and palmitoylethanolamide. Int J Mol Sci. 2021;22(3):1034. DOI: 10.3390/ijms22031034Higuchi N., Hira T., Yamada N., Hara H. Oral administration of corn zein hydrolysate stimulates GLP-1 and GIP secretion and improves glucose tolerance in male normal rats and Goto-Kakizaki rats // Endocrinology. – 2013. – Vol. 154, No. 9. – P. 3089–3098. DOI: 10.1210/en.2012-2275Higuchi N, Hira T, Yamada N, Hara H. Oral administration of corn zein hydrolysate stimulates GLP-1 and GIP secretion and improves glucose tolerance in male normal rats and Goto-Kakizaki rats. Endocrinology. 2013;154(9):3089–98. DOI: 10.1210/en.2012-2275Gagnon J., Baggio L.L., Drucker D.J., Brubaker P.L. Ghrelin Is a Novel Regulator of GLP-1 Secretion // Diabetes. – 2015. – Vol. 64, No. 5. – P. 1513–1521. DOI: 10.2337/db14-1176Gagnon J, Baggio LL, Drucker DJ, Brubaker PL. Ghrelin Is a Novel Regulator of GLP-1 Secretion. Diabetes. 2015;64(5):1513–21. DOI: 10.2337/db14-1176Hansen L., Lampert S., Mineo H., Holst J.J. Neural regulation of glucagon-like peptide-1 secretion in pigs // Am J Physiol Endocrinol Metab. – 2004. – Vol. 287, No. 5. – P. E939–947. DOI: 10.1152/ajpendo.00197.2004Hansen L, Lampert S, Mineo H, Holst JJ. Neural regulation of glucagon-like peptide-1 secretion in pigs. Am J Physiol Endocrinol Metab. 2004;287(5):E939–947. DOI: 10.1152/ajpendo.00197.2004Persson K., Gingerich R.L., Nayak S., Wada K., Wada E., Ahrén B. Reduced GLP-1 and insulin responses and glucose intolerance after gastric glucose in GRP receptor-deleted mice // Am J Physiol Endocrinol. Metab. – 2000. – Vol. 279, No. 5. – P. E956–962. DOI: 10.1152/ajpendo.2000.279.5.E956Persson K, Gingerich RL, Nayak S, Wada K, Wada E, Ahrén B. Reduced GLP-1 and insulin responses and glucose intolerance after gastric glucose in GRP receptor-deleted mice. Am J Physiol Endocrinol. Metab. 2000;279(5):E956–962. DOI: 10.1152/ajpendo.2000.279.5.E956Han Y.E., Kang C.W., Oh J.H., Park S.H., Ku C.R., Cho Y.H., Lee M.K., Lee E.J. Olfactory Receptor OR51E1 Mediates GLP-1 Secretion in Human and Rodent Enteroendocrine L Cells // J Endocr Soc. – 2018. – Vol. 2, No. 11. – P. 1251–1258. DOI: 10.1210/js.2018-00165Han YE, Kang CW, Oh JH, Park SH, Ku CR, Cho YH, Lee MK, Lee EJ. Olfactory receptor OR51E1 mediates GLP-1 secretion in human and rodent enteroendocrine L cells. J Endocr Soc. 2018;2(11):1251–8. DOI: 10.1210/js.2018-00165Tomas A., Jones B., Leech C. New Insights into Beta-Cell GLP-1 Receptor and cAMP Signaling // J Mol Biol. – 2020. – Vol. 432, No. 5. – P. 1347–1366. DOI: 10.1016/j.jmb.2019.08.009Tomas A, Jones B, Leech C. New Insights into Beta-Cell GLP-1 Receptor and cAMP Signaling. J Mol Biol. 2020;432(5):1347–66. DOI: 10.1016/j.jmb.2019.08.009Gromada J., Brock B., Schmitz O., Rorsman P. Glucagon-like peptide-1: regulation of insulin secretion and therapeutic potential // Basic Clin Pharmacol Toxicol. – 2004. – Vol. 95, No. 6. – P. 252–262. DOI: 10.1111/j.1742-7843.2004.t01-1-pto950502.xGromada J, Brock B, Schmitz O, Rorsman P. Glucagon-like peptide-1: regulation of insulin secretion and therapeutic potential. Basic Clin Pharmacol Toxicol. – 2004;95(6):252–262. DOI: 10.1111/j.1742-7843.2004.t01-1-pto950502.xButeau J. GLP-1 receptor signaling: effects on pancreatic beta-cell proliferation and survival // Diabetes Metab. – 2008. – Vol. 34 Suppl 2. – P. S73–77. DOI: 10.1016/S1262-3636(08)73398-6Buteau J. GLP-1 receptor signaling: effects on pancreatic beta-cell proliferation and survival. Diabetes Metab. 2008;34(Suppl 2):S73–77. DOI: 10.1016/S1262-3636(08)73398-6Park S., Dong X., Fisher T.L., Dunn S., Omer A.K., Weir G., White M.F. Exendin-4 uses Irs2 signaling to mediate pancreatic beta cell growth and function // J Biol Chem. – 2006. – Vol. 281, No. 2. – P. 1159–1168. DOI: 10.1074/jbc.M508307200Park S, Dong X, Fisher TL, Dunn S, Omer AK, Weir G, White MF. Exendin-4 uses Irs2 signaling to mediate pancreatic beta cell growth and function. J Biol Chem. 2006;281(2):1159–68. DOI: 10.1074/jbc.M508307200Peng W., Zhou R., Sun Z.F., Long J.W., Gong Y.Q. Novel Insights into the Roles and Mechanisms of GLP-1 Receptor Agonists against Aging-Related Diseases // Aging Dis. – 2022. – Vol. 13, No. 2. – P. 468–490. DOI: 10.14336/AD.2021.0928Peng W, Zhou R, Sun ZF, Long JW, Gong YQ. Novel insights into the roles and mechanisms of GLP-1 receptor agonists against aging-related diseases. Aging Dis. 2022;13(2):468–90. DOI: 10.14336/AD.2021.0928Oh Y.S., Jun H.S. Effects of Glucagon-Like Peptide-1 on Oxidative Stress and Nrf2 Signaling // Int J Mol Sci. – 2017. – Vol. 19, No. 1. – P. 26. DOI: 10.3390/ijms19010026Oh YS, Jun HS. Effects of glucagon-like peptide-1 on oxidative stress and Nrf2 signaling. Int J Mol Sci. 2017;19(1):26. DOI: 10.3390/ijms19010026Urusova I.A., Farilla L., Hui H., D’Amico E., Perfetti R. GLP-1 inhibition of pancreatic islet cell apoptosis // Trends Endocrinol Metab. – 2004. – Vol. 15, No. 1. – P. 27–33. DOI: 10.1016/j.tem.2003.11.006Urusova IA, Farilla L, Hui H, D’Amico E, Perfetti R. GLP-1 inhibition of pancreatic islet cell apoptosis. Trends Endocrinol Metab. – 2004;15(1):27–33. DOI: 10.1016/j.tem.2003.11.006Drucker D.J. Mechanisms of action and therapeutic application of glucagon-like peptide-1 // Cell Metab. – 2018. – Vol. 27, No. 4. – P. 740–756. DOI: 10.1016/j.cmet.2018.03.001Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metab. 2018;27(4):740–56. DOI: 10.1016/j.cmet.2018.03.001De Marinis Y.Z., Salehi A., Ward C.E., Zhang Q., Abdulkader F., Bengtsson M., Braha O., Braun M., Ramracheya R., Amisten S., Habib A.M., Moritoh Y., Zhang E., Reimann F., Rosengren A., Shibasaki T., Gribble F., Renström E., Seino S., Eliasson L., Rorsman P. GLP-1 inhibits and adrenaline stimulates glucagon release by differential modulation of N– and L-type Ca2+ channel-dependent exocytosis // Cell Metab. – 2010. – Vol. 11, No. 6. – P. 543–553. DOI: 10.1016/j.cmet.2010.04.007De Marinis YZ, Salehi A, Ward CE, Zhang Q, Abdulkader F, Bengtsson M, Braha O, Braun M, Ramracheya R, Amisten S, Habib AM, Moritoh Y, Zhang E, Reimann F, Rosengren A, Shibasaki T, Gribble F, Renström E, Seino S, Eliasson L, Rorsman P. GLP-1 inhibits and adrenaline stimulates glucagon release by differential modulation of N- and L-type Ca2+ channel-dependent exocytosis. Cell Metab. 2010;11(6):543–53. DOI: 10.1016/j.cmet.2010.04.007Ravassa S., Zudaire A., Díez J. GLP-1 and cardioprotection: from bench to bedside // Cardiovasc Res. – 2012. – Vol. 94, No. 2. – P. 316–323. DOI: 10.1093/cvr/cvs123Ravassa S, Zudaire A, Díez J. GLP-1 and cardioprotection: from bench to bedside. Cardiovasc Res. 2012;94(2):316–23. DOI: 10.1093/cvr/cvs123Bremholm L., Andersen U.B., Hornum M., Hilsted L., Veedfald S., Hartmann B., Holst J.J. Acute effects of glucagon-like peptide-1, GLP-19-36 amide, and exenatide on mesenteric blood flow, cardiovascular parameters, and biomarkers in healthy volunteers // Physiol Rep. – 2017. – Vol. 5, No. 4. – P. e13102. DOI: 10.14814/phy2.13102Bremholm L, Andersen U.B, Hornum M, Hilsted L, Veedfald S, Hartmann B, Holst J.J. Acute effects of glucagon-like peptide-1, GLP-19-36 amide, and exenatide on mesenteric blood flow, cardiovascular parameters, and biomarkers in healthy volunteers. Physiol Rep. 2017;5(4):e13102. DOI: 10.14814/phy2.13102Sun F., Wu S., Guo S., Yu K., Yang Z., Li L., Zhang Y., Quan X., Ji L., Zhan S. Impact of GLP-1 receptor agonists on blood pressure, heart rate and hypertension among patients with type 2 diabetes: A systematic review and network meta-analysis // Diabetes Res Clin Pract. – 2015. – Vol. 110, No. 1. – P. 26–37. DOI: 10.1016/j.diabres.2015.07.015Sun F, Wu S, Guo S, Yu K, Yang Z, Li L, Zhang Y, Quan X, Ji L, Zhan S. Impact of GLP-1 receptor agonists on blood pressure, heart rate and hypertension among patients with type 2 diabetes: A systematic review and network meta-analysis. Diabetes Res Clin Pract. 2015;110(1):26–37. DOI: 10.1016/j.diabres.2015.07.015Erbil D., Eren C.Y., Demirel C., Küçüker M.U., Solaroğlu I., Eser H.Y. GLP-1’s role in neuroprotection: a systematic review // Brain Inj. – 2019. – Vol. 33, No. 6. – P. 734–819. DOI: 10.1080/02699052.2019.1587000Erbil D, Eren CY, Demirel C, Küçüker MU, Solaroğlu I, Eser HY. GLP-1’s role in neuroprotection: a systematic review. Brain Inj. 2019;33(6):734–819. DOI: 10.1080/02699052.2019.1587000Heppner K.M., Kirigiti M., Secher A., Paulsen S.J., Buckingham R., Pyke C., Knudsen L.B., Vrang N., Grove K.L. Expression and distribution of glucagon-like peptide-1 receptor mRNA, protein and binding in the male nonhuman primate (Macaca mulatta) brain // Endocrinology. – 2015. – Vol. 156, No. 1. – P. 255–267. DOI: 10.1210/en.2014-1675Heppner KM, Kirigiti M, Secher A, Paulsen SJ, Buckingham R, Pyke C, Knudsen LB, Vrang N, Grove KL. Expression and distribution of glucagon-like peptide-1 receptor mRNA, protein and binding in the male nonhuman primate (Macaca mulatta) brain. Endocrinology. 2015;156(1):255–67. DOI: 10.1210/en.2014-1675Kabahizi A., Wallace B., Lieu L., Chau D., Dong Y., Hwang E.S., Williams K.W. Glucagon-like peptide-1 (GLP-1) signalling in the brain: From neural circuits and metabolism to therapeutics // Br J Pharmacol. – 2022. – Vol. 179, No. 4. – P. 600–624. DOI: 10.1111/bph.15682Kabahizi A, Wallace B, Lieu L, Chau D, Dong Y, Hwang ES, Williams KW. Glucagon-like peptide-1 (GLP-1) signalling in the brain: From neural circuits and metabolism to therapeutics. Br J Pharmacol. 2022;179(4):600–24. DOI: 10.1111/bph.15682Trapp S., Brierley D.I. Brain GLP-1 and the regulation of food intake: GLP-1 action in the brain and its implications for GLP-1 receptor agonists in obesity treatment // Br J Pharmacol. – 2022. – Vol. 179, No. 4. – P. 557–570. DOI: 10.1111/bph.15638Trapp S, Brierley DI. Brain GLP-1 and the regulation of food intake: GLP-1 action in the brain and its implications for GLP-1 receptor agonists in obesity treatment. Br J Pharmacol. 2022;179(4):557–70. DOI: 10.1111/bph.15638Alhadeff A.L., Mergler B.D., Zimmer D.J., Turner C.A., Reiner D.J., Schmidt H.D., Grill H.J., Hayes M.R. Endogenous glucagon-like peptide-1 receptor signaling in the nucleus tractus solitarius is required for food intake control // Neuropsychopharmacology. – 2017. – Vol. 42, No. 7. – P. 1471–1479. DOI: 10.1038/npp.2016.246Alhadeff AL, Mergler BD, Zimmer DJ, Turner CA, Reiner DJ, Schmidt HD, Grill HJ, Hayes MR. Endogenous glucagon-like peptide-1 receptor signaling in the nucleus tractus solitarius is required for food intake control. Neuropsychopharmacology. 2017;42(7):1471–9. DOI: 10.1038/npp.2016.246Ong Z.Y., Liu J.J., Pang Z.P., Grill H.J. Paraventricular thalamic control of food intake and reward: role of glucagon-like peptide-1 receptor signaling // Neuropsychopharmacology. – 2017. – Vol. 42, No. 12. – P. 2387–2397. DOI: 10.1038/npp.2017.150Ong ZY, Liu JJ, Pang ZP, Grill HJ. Paraventricular thalamic control of food intake and reward: role of glucagon-like peptide-1 receptor signaling. Neuropsychopharmacology. 2017;42(12):2387–97. DOI: 10.1038/npp.2017.150Adams J.M., Pei H., Sandoval D.A., Seeley R.J., Chang R.B., Liberles S.D., Olson D.P. Liraglutide modulates appetite and body weight through glucagon-like peptide 1 receptor-expressing glutamatergic neurons // Diabetes. – 2018. – Vol. 67, No. 8. – P. 1538–1548. DOI: 10.2337/db17-1385Adams JM, Pei H, Sandoval DA, Seeley RJ, Chang RB, Liberles SD, Olson DP. Liraglutide modulates appetite and body weight through glucagon-like peptide 1 receptor-expressing glutamatergic neurons. Diabetes. 2018;67(8):1538–48. DOI: 10.2337/db17-1385Hayes M.R., Leichner T.M., Zhao S., Lee G.S., Chowansky A., Zimmer D., De Jonghe B.C., Kanoski S.E., Grill H.J., Bence K.K. Intracellular signals mediating the food intake-suppressive effects of hindbrain glucagon-like peptide-1 receptor activation // Cell Metab. – 2011. – Vol. 13, No. 3. – P. 320–330. DOI: 10.1016/j.cmet.2011.02.001Hayes MR, Leichner TM, Zhao S, Lee GS, Chowansky A, Zimmer D, De Jonghe BC, Kanoski SE, Grill HJ, Bence KK. Intracellular signals mediating the food intake-suppressive effects of hindbrain glucagon-like peptide-1 receptor activation. Cell Metab. 2011;13(3):320–30. DOI: 10.1016/j.cmet.2011.02.001Sirohi S., Schurdak J.D., Seeley R.J., Benoit S.C., Davis J.F. Central & peripheral glucagon-like peptide-1 receptor signaling differentially regulate addictive behaviors // Physiol Behav. – 2016. – Vol. 161. – P. 140–144. DOI: 10.1016/j.physbeh.2016.04.013Sirohi S, Schurdak JD, Seeley RJ, Benoit SC, Davis JF. Central & peripheral glucagon-like peptide-1 receptor signaling differentially regulate addictive behaviors. Physiol Behav. 2016;161:140–4. DOI: 10.1016/j.physbeh.2016.04.013Dossat A.M., Diaz R., Gallo L., Panagos A., Kay K., Williams D.L. Nucleus accumbens GLP-1 receptors influence meal size and palatability // Am J Physiol Endocrinol Metab. – 2013. – Vol. 304, No. 12. – P. E1314–1320. DOI: 10.1152/ajpendo.00137.2013Dossat AM, Diaz R, Gallo L, Panagos A, Kay K, Williams DL. Nucleus accumbens GLP-1 receptors influence meal size and palatability. Am J Physiol Endocrinol Metab. 2013;304(12):E1314–1320. DOI: 10.1152/ajpendo.00137.2013Hisadome K., Reimann F., Gribble F.M., Trapp S. CCK stimulation of GLP-1 neurons involves α1-adrenoceptor-mediated increase in glutamatergic synaptic inputs // Diabetes. – 2011. – Vol. 60, No. 11. – P. 2701–2709. DOI: 10.2337/db11-0489Hisadome K, Reimann F, Gribble FM, Trapp S. CCK stimulation of GLP-1 neurons involves α1-adrenoceptor-mediated increase in glutamatergic synaptic inputs. Diabetes. 2011;60(11):2701–9. DOI: 10.2337/db11-0489Gaykema R.P., Newmyer B.A., Ottolini M., Raje V., Warthen D.M., Lambeth P.S., Niccum M., Yao T., Huang Y., Schulman I.G., Harris T.E., Patel M.K., Williams K.W., Scott M.M. Activation of murine pre-proglucagon-producing neurons reduces food intake and body weight // J Clin Invest. – 2017. – Vol. 127, No. 3. – P. 1031–1045. DOI: 10.1172/JCI81335Gaykema RP, Newmyer BA, Ottolini M, Raje V, Warthen DM, Lambeth PS, Niccum M, Yao T, Huang Y, Schulman IG, Harris TE, Patel MK, Williams KW, Scott MM. Activation of murine pre-proglucagon-producing neurons reduces food intake and body weight. J Clin Invest. 2017;127(3):1031–45. DOI: 10.1172/JCI81335Holt M.K., Richards J.E., Cook D.R., Brierley D.I., Williams D.L., Reimann F., Gribble F.M., Trapp S. Preproglucagon neurons in the nucleus of the solitary tract are the main source of brain GLP-1, mediate stress-induced hypophagia, and limit unusually large intakes of food // Diabetes. – 2019. – Vol. 68, No. 1. – P. 21–33. DOI: 10.2337/db18-0729Holt MK, Richards JE, Cook DR, Brierley DI, Williams DL, Reimann F, Gribble FM, Trapp S. Preproglucagon neurons in the nucleus of the solitary tract are the main source of brain GLP-1, mediate stress-induced hypophagia, and limit unusually large intakes of food. Diabetes. 2019;68(1):21–33. DOI: 10.2337/db18-0729Lee S.J., Sanchez-Watts G., Krieger J.P., Pignalosa A., Norell P.N., Cortella A., Pettersen K.G., Vrdoljak D., Hayes M.R., Kanoski S.E., Langhans W., Watts A.G. Loss of dorsomedial hypothalamic GLP-1 signaling reduces BAT thermogenesis and increases adiposity // Mol Metab. – 2018. – Vol. 11. – P. 33–46. DOI: 10.1016/j.molmet.2018.03.008Lee SJ, Sanchez-Watts G, Krieger JP, Pignalosa A, Norell PN, Cortella A, Pettersen KG, Vrdoljak D, Hayes MR, Kanoski SE, Langhans W, Watts AG. Loss of dorsomedial hypothalamic GLP-1 signaling reduces BAT thermogenesis and increases adiposity. Mol Metab. 2018;11:33–46. DOI: 10.1016/j.molmet.2018.03.008Maselli D.B., Camilleri M. Effects of GLP-1 and Its Analogs on Gastric Physiology in Diabetes Mellitus and Obesity // Adv Exp Med Biol. – 2021. – Vol. 1307. – P. 171–192. DOI: 10.1007/5584_2020_496Maselli DB, Camilleri M. Effects of GLP-1 and Its Analogs on Gastric Physiology in Diabetes Mellitus and Obesity. Adv Exp Med Biol. 2021;1307:171–92. DOI: 10.1007/5584_2020_496Ghosal S., Packard A.E.B., Mahbod P., McKlveen J.M., Seeley R.J., Myers B., Ulrich-Lai Y., Smith E.P., D’Alessio D.A., Herman J.P. Disruption of Glucagon-Like Peptide 1 Signaling in Sim1 Neurons Reduces Physiological and Behavioral Reactivity to Acute and Chronic Stress // J Neurosci. – 2017. – Vol. 37, No. 1. – P. 184–193. DOI: 10.1523/JNEUROSCI.1104-16.2016Ghosal S, Packard AEB, Mahbod P, McKlveen JM, Seeley RJ, Myers B, Ulrich-Lai Y, Smith EP, D’Alessio DA, Herman JP. Disruption of glucagon-like peptide 1 signaling in sim1 neurons reduces physiological and behavioral reactivity to acute and chronic stress. J Neurosci. 2017;37(1):184–93. DOI: 10.1523/JNEUROSCI.1104-16.2016Salcedo I., Tweedie D., Li Y., Greig N.H. Neuroprotective and neurotrophic actions of glucagon-like peptide-1: an emerging opportunity to treat neurodegenerative and cerebrovascular disorders // Br J Pharmacol. – 2012. – Vol. 166, No. 5. – P. 1586–1599. DOI: 10.1111/j.1476-5381.2012.01971.xSalcedo I, Tweedie D, Li Y, Greig NH. Neuroprotective and neurotrophic actions of glucagon-like peptide-1: an emerging opportunity to treat neurodegenerative and cerebrovascular disorders. Br J Pharmacol. 2012;166(5):1586–99. DOI: 10.1111/j.1476-5381.2012.01971.xMonti G., Gomes Moreira D., Richner M., Mutsaers H.A.M., Ferreira N., Jan A. GLP-1 Receptor Agonists in Neurodegeneration: Neurovascular Unit in the Spotlight // Cells. – 2022. – Vol. 11, No. 13. – P. 2023. DOI: 10.3390/cells11132023Monti G, Gomes Moreira D, Richner M, Mutsaers HAM, Ferreira N, Jan A. GLP-1 receptor agonists in neurodegeneration: neurovascular unit in the spotlight. Cells. 2022;11(13):2023. DOI: 10.3390/cells11132023Chang C.C., Lin T.C., Ho H.L., Kuo C.Y., Li H.H., Korolenko T.A., Chen W.J., Lai T.J., Ho Y.J., Lin C.L. GLP-1 Analogue Liraglutide Attenuates Mutant Huntingtin-Induced Neurotoxicity by Restoration of Neuronal Insulin Signaling // Int J Mol Sci. – 2018. – Vol. 19, No. 9. – P. 2505. DOI: 10.3390/ijms19092505Chang CC, Lin TC, Ho HL, Kuo CY, Li HH, Korolenko TA, Chen WJ, Lai TJ, Ho YJ, Lin CL. GLP-1 analogue liraglutide attenuates mutant huntingtin-induced neurotoxicity by restoration of neuronal insulin signaling. Int J Mol Sci. 2018;19(9):2505. DOI: 10.3390/ijms19092505Qi L., Ke L., Liu X., Liao L., Ke S., Liu X., Wang Y., Lin X., Zhou Y., Wu L., Chen Z., Liu L. Subcutaneous administration of liraglutide ameliorates learning and memory impairment by modulating tau hyperphosphorylation via the glycogen synthase kinase-3β pathway in an amyloid β protein induced alzheimer disease mouse model // Eur J Pharmacol. – 2016. – Vol. 783. – P. 23–32. DOI: 10.1016/j.ejphar.2016.04.052Qi L, Ke L, Liu X, Liao L, Ke S, Liu X, Wang Y, Lin X, Zhou Y, Wu L, Chen Z, Liu L. Subcutaneous administration of liraglutide ameliorates learning and memory impairment by modulating tau hyperphosphorylation via the glycogen synthase kinase-3β pathway in an amyloid β protein induced Alzheimer disease mouse model. Eur J Pharmacol. 2016;783:23–32. DOI: 10.1016/j.ejphar.2016.04.052Chen S., Sun J., Zhao G., Guo A., Chen Y., Fu R., Deng Y. Liraglutide Improves Water Maze Learning and Memory Performance While Reduces Hyperphosphorylation of Tau and Neurofilaments in APP/PS1/Tau Triple Transgenic Mice // Neurochem Res. – 2017. – Vol. 42, No. 8. – P. 2326–2335. DOI: 10.1007/s11064-017-2250-8Chen S, Sun J, Zhao G, Guo A, Chen Y, Fu R, Deng Y. Liraglutide improves water maze learning and memory performance while reduces hyperphosphorylation of tau and neurofilaments in APP/PS1/Tau triple transgenic mice. Neurochem Res. 2017;42(8):2326–35. DOI: 10.1007/s11064-017-2250-8Hansen H.H., Fabricius K., Barkholt P., Niehoff M.L., Morley J.E., Jelsing J., Pyke C., Knudsen L.B., Farr S.A., Vrang N. The GLP-1 Receptor Agonist Liraglutide Improves Memory Function and Increases Hippocampal CA1 Neuronal Numbers in a Senescence-Accelerated Mouse Model of Alzheimer’s Disease // J Alzheimers Dis. – 2015. – Vol. 46, No. 4. – P. 877–888. DOI: 10.3233/JAD-143090Hansen HH, Fabricius K, Barkholt P, Niehoff ML, Morley JE, Jelsing J, Pyke C, Knudsen LB, Farr SA, Vrang N. The GLP-1 receptor agonist liraglutide improves memory function and increases hippocampal ca1 neuronal numbers in a senescence-accelerated mouse model of Alzheimer’s disease. J Alzheimers Dis. 2015;46(4):877–88. DOI: 10.3233/JAD-143090Gejl M., Brock B., Egefjord L., Vang K., Rungby J., Gjedde A. Blood-Brain Glucose Transfer in Alzheimer’s disease: Effect of GLP-1 Analog Treatment // Sci Rep. – 2017. – Vol. 7, No. 1. – P. 17490. DOI: 10.1038/s41598-017-17718-yGejl M, Brock B, Egefjord L, Vang K, Rungby J, Gjedde A. Blood-brain glucose transfer in Alzheimer’s disease: effect of GLP-1 analog treatment. Sci Rep. 2017;7(1):17490. DOI: 10.1038/s41598-017-17718-yWatson K.T., Wroolie T.E., Tong G., Foland-Ross L.C., Frangou S., Singh M., McIntyre R.S., Roat-Shumway S., Myoraku A., Reiss A.L., Rasgon N.L. Neural correlates of liraglutide effects in persons at risk for Alzheimer’s disease // Behav Brain Res. – 2019. – Vol. 356. – P. 271–278. DOI: 10.1016/j.bbr.2018.08.006Watson KT, Wroolie TE, Tong G, Foland-Ross LC, Frangou S, Singh M, McIntyre RS, Roat-Shumway S, Myoraku A, Reiss AL, Rasgon NL. Neural correlates of liraglutideeffects in persons at risk for Alzheimer’s disease. Behav Brain Res. 2019;356:271–8. DOI: 10.1016/j.bbr.2018.08.006Femminella G.D., Frangou E., Love S.B., Busza G., Holmes C., Ritchie C., Lawrence R., McFarlane B., Tadros G., Ridha B.H., Bannister C., Walker Z., Archer H., Coulthard E., Underwood B.R., Prasanna A., Koranteng P., Karim S., Junaid K., McGuinness B., Nilforooshan R., Macharouthu A., Donaldson A., Thacker S., Russell G., Malik N., Mate V., Knight L., Kshemendran S., Harrison J., Hölscher C., Brooks D.J., Passmore A.P., Ballard C., Edison P. Evaluating the effects of the novel GLP-1 analogue liraglutide in Alzheimer’s disease: study protocol for a randomised controlled trial (ELAD study) // Trials. – 2019. – Vol. 20, No. 1. – P. 191. DOI: 10.1186/s13063-019-3259-xFemminella GD, Frangou E, Love SB, Busza G, Holmes C, Ritchie C, Lawrence R, McFarlane B, Tadros G, Ridha BH, Bannister C, Walker Z, Archer H, Coulthard E, Underwood BR, Prasanna A, Koranteng P, Karim S, Junaid K, McGuinness B, Nilforooshan R, Macharouthu A, Donaldson A, Thacker S, Russell G, Malik N, Mate V, Knight L, Kshemendran S, Harrison J, Hölscher C, Brooks DJ, Passmore AP, Ballard C, Edison P. Evaluating the effects of the novel GLP-1 analogue liraglutide in Alzheimer’s disease: study protocol for a randomised controlled trial (ELAD study). Trials. 2019;20(1):191. DOI: 10.1186/s13063-019-3259-xLi Y., Perry T., Kindy M.S., Harvey B.K., Tweedie D., Holloway H.W., Powers K., Shen H., Egan J.M., Sambamurti K., Brossi A., Lahiri D.K., Mattson M.P., Hoffer B.J., Wang Y., Greig N.H. GLP-1 receptor stimulation preserves primary cortical and dopaminergic neurons in cellular and rodent models of stroke and Parkinsonism // Proc Natl Acad Sci USA. – 2009. – Vol. 106, No. 4. – P. 1285–1290. DOI: 10.1073/pnas.0806720106Li Y, Perry T, Kindy MS, Harvey BK, Tweedie D, Holloway HW, Powers K, Shen H, Egan JM, Sambamurti K, Brossi A, Lahiri DK, Mattson MP, Hoffer BJ, Wang Y, Greig NH. GLP-1 receptor stimulation preserves primary cortical and dopaminergic neurons in cellular and rodent models of stroke and Parkinsonism. Proc Natl Acad Sci USA. 2009;106(4):1285–90. DOI: 10.1073/pnas.0806720106Rampersaud N., Harkavyi A., Giordano G., Lever R., Whitton J., Whitton P.S. Exendin-4 reverses biochemical and behavioral deficits in a pre-motor rodent model of Parkinson’s disease with combined noradrenergic and serotonergic lesions // Neuropeptides. – 2012. – Vol. 46, No. 5. – P. 183–193. DOI: 10.1016/j.npep.2012.07.004Rampersaud N, Harkavyi A, Giordano G, Lever R, Whitton J, Whitton PS. Exendin-4 reverses biochemical and behavioral deficits in a pre-motor rodent model of Parkinson’s disease with combined noradrenergic and serotonergic lesions. Neuropeptides. 2012;46(5):183–93. DOI: 10.1016/j.npep.2012.07.004Athauda D., Maclagan K., Skene S.S., Bajwa-Joseph M., Letchford D., Chowdhury K., Hibbert S., Budnik N., Zampedri L., Dickson J., Li .Y, Aviles-Olmos I., Warner T.T., Limousin P., Lees A.J., Greig N.H., Tebbs S., Foltynie T. Exenatide once weekly versus placebo in Parkinson’s disease: a randomised, double-blind, placebo-controlled trial // Lancet. – 2017. – Vol. 390, No. 10103. – P. 1664–1675. DOI: 10.1016/S0140-6736(17)31585-4Athauda D, Maclagan K, Skene SS, Bajwa-Joseph M, Letchford D, Chowdhury K, Hibbert S, Budnik N, Zampedri L, Dickson J, Li Y, Aviles-Olmos I, Warner TT, Limousin P, Lees AJ, Greig NH, Tebbs S, Foltynie T. Exenatide once weekly versus placebo in Parkinson’s disease: a randomised, double-blind, placebo-controlled trial. Lancet. 2017;390(10103):1664–75. DOI: 10.1016/S0140-6736(17)31585-4Basalay M.V., Davidson S.M., Yellon D.M. Neuroprotection in Rats Following Ischaemia-Reperfusion Injury by GLP-1 Analogues-Liraglutide and Semaglutide // Cardiovasc Drugs Ther. – 2019. – Vol. 33, No. 6. – P. 661–667. DOI: 10.1007/s10557-019-06915-8Basalay MV, Davidson SM, Yellon DM. Neuroprotection in rats following ischaemia-reperfusion injury by GLP-1 analogues-liraglutide and semaglutide. cardiovasc. Drugs Ther. 2019;33(6):661–7. DOI: 10.1007/s10557-019-06915-8Gerstein H.C., Colhoun H.M., Dagenais G.R., Diaz R., Lakshmanan M., Pais P., Probstfield J., Botros F.T., Riddle M.C., Rydén L., Xavier D., Atisso C.M., Dyal L., Hall S., Rao-Melacini P., Wong G., Avezum A., Basile J., Chung N., Conget I., Cushman W.C., Franek E., Hancu N., Hanefeld M., Holt S., Jansky P., Keltai M., Lanas F., Leiter L.A., Lopez-Jaramillo P., Cardona Munoz E.G., Pirags V., Pogosova N., Raubenheimer P.J., Shaw J.E., Sheu W.H., Temelkova-Kurktschiev T.; REWIND Investigators. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial // Lancet. – 2019. – Vol. 394, No. 10193. – P. 131–138. DOI: 10.1016/S0140-6736(19)31150-XGerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, Probstfield J, Botros FT, Riddle MC, Rydén L, Xavier D, Atisso CM, Dyal L, Hall S, Rao-Melacini P, Wong G, Avezum A, Basile J, Chung N, Conget I, Cushman WC, Franek E, Hancu N, Hanefeld M, Holt S, Jansky P, Keltai M, Lanas F, Leiter LA, Lopez-Jaramillo P, Cardona Munoz EG, Pirags V, Pogosova N, Raubenheimer PJ, Shaw JE, Sheu WH, Temelkova-Kurktschiev T; REWIND Investigators. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial. Lancet. 2019;394(10193):131–8. DOI: 10.1016/S0140-6736(19)31150-XHansen M.S., Frost M. Alliances of the gut and bone axis // Semin Cell Dev Biol. – 2022. – Vol. 123. – P. 74–81. DOI: 10.1016/j.semcdb.2021.06.024Hansen MS, Frost M. Alliances of the gut and bone axis. Semin Cell Dev Biol. 2022;123):74–81. DOI: 10.1016/j.semcdb.2021.06.024Mieczkowska A., Mansur S., Bouvard B., Flatt P.R., Thorens B., Irwin N., Chappard D., Mabilleau G. Double incretin receptor knock-out (DIRKO) mice present with alterations of trabecular and cortical micromorphology and bone strength // Osteoporos Int. – 2015. – Vol. 26, No. 1. – P. 209–218. DOI: 10.1007/s00198-014-2845-8Mieczkowska A, Mansur S, Bouvard B, Flatt PR, Thorens B, Irwin N, Chappard D, Mabilleau G. Double incretin receptor knock-out (DIRKO) mice present with alterations of trabecular and cortical micromorphology and bone strength. Osteoporos Int. 2015;26(1):209–18. DOI: 10.1007/s00198-014-2845-8Maagensen H., Helsted M.M., Gasbjerg L.S., Vilsbøll T., Knop F.K. The Gut-Bone Axis in Diabetes // Curr Osteoporos Rep. – 2022. DOI: 10.1007/s11914-022-00767-2Maagensen H, Helsted MM, Gasbjerg LS, Vilsbøll T, Knop FK. The Gut-Bone Axis in Diabetes. Curr Osteoporos Rep. 2022. DOI: 10.1007/s11914-022-00767-2Nauck M.A., Quast D.R., Wefers J., Meier J.J. GLP-1 receptor agonists in the treatment of type 2 diabetes – state-of-the-art // Mol Metab. – 2021. – Vol. 46. – P. 101102. DOI: 10.1016/j.molmet.2020.101102Nauck MA, Quast DR, Wefers J, Meier JJ. GLP-1 receptor agonists in the treatment of type 2 diabetes – state-of-the-art. Mol Metab. 2021;46:101102. DOI: 10.1016/j.molmet.2020.101102Tomlinson B., Hu M., Zhang Y., Chan P., Liu Z.M. An overview of new GLP-1 receptor agonists for type 2 diabetes // Expert Opin Investig Drugs. – 2016. – Vol. 25, No. 2. – P. 145–158. DOI: 10.1517/13543784.2016.1123249Tomlinson B, Hu M, Zhang Y, Chan P, Liu ZM. An overview of new GLP-1 receptor agonists for type 2 diabetes. Expert Opin Investig Drugs. 2016;25(2):145–58. DOI: 10.1517/13543784.2016.1123249Yang X., Qiang Q., Li N., Feng P., Wei W., Hölscher C. Neuroprotective Mechanisms of Glucagon-Like Peptide-1-Based Therapies in Ischemic Stroke: An Update Based on Preclinical Research // Front Neurol. – 2022. – Vol. 13. – P. 844697. DOI: 10.3389/fneur.2022.844697Yang X, Qiang Q, Li N, Feng P, Wei W, Hölscher C. Neuroprotective Mechanisms of Glucagon-Like Peptide-1-Based Therapies in Ischemic Stroke: An Update Based on Preclinical Research. Front Neurol. 2022;13:844697. DOI: 10.3389/fneur.2022.844697Cheang J.Y., Moyle P.M. Glucagon-Like Peptide-1 (GLP-1)-based therapeutics: current status and future opportunities beyond Type 2 Diabetes // ChemMedChem. – 2018. – Vol. 13, No. 7. – P. 662–671. DOI: 10.1002/cmdc.201700781Cheang JY, Moyle PM. Glucagon-like peptide-1 (GLP-1)-based therapeutics: current status and future opportunities beyond Type 2 Diabetes. Chem Med Chem. 2018;13(7):662–71. DOI: 10.1002/cmdc.201700781Kalra S., Bhattacharya S., Kapoor N. Contemporary classification of glucagon-like peptide 1 receptor Agonists (GLP1RAs) // Diabetes Ther. – 2021. – Vol. 12, No. 8. – P. 2133–2147. DOI: 10.1007/s13300-021-01113-yKalra S, Bhattacharya S, Kapoor N. Contemporary classification of glucagon-like peptide 1 receptor Agonists (GLP1RAs). Diabetes Ther. 2021;12(8):2133–47. DOI: 10.1007/s13300-021-01113-yАметов А.С., Шохин И.Е., Рогожина Е.А., Бодрова Т.Г., Невретдинова М.Е., Белый П.А., Заславская К.Я., Куркин Д.В., Корянова К.Н., Мищенко Е.С., Носков С.М. Российская разработка для лекарственной независимости в эндокринологии: сравнительный анализ биоэквивалентности, безопасности и переносимости первого отечественного лираглутида // Фармация и фармакология. – 2023. – Т. 11, № 3. – С. 255–276. DOI: 10.19163/2307-9266-2023-11-3-255-276Ametov AS, Shokhin IE, Rogozhina EA, Bodrova TG, Nevretdinova ME, Bely PA, Zaslavskaya KYa, Kurkin DV, Koryanova KN, Mishchenko ES, Noskov SM. Russian development for drug independence in endocrinology: comparative analysis of bioequivalence, safety and tolerability of the first domestic liraglutide. Pharmacy & Pharmacology. 2023;11(3):255–76. DOI: 10.19163/2307-9266-2023-11-3-255-276Арефьева А.Н, Банко В.В., Садовских М.О., Носков С.М. Первый препарат семаглутида в Российской Федерации: результаты открытого рандомизированного исследования фармакокинетики // Медицинский совет. – 2023. – Т. 17, № 16. – С. 77–82. DOI: 10.21518/ms2023-312Arefeva AN, Banko VV, Sadovskikh MO, Noskov SM. Pharmacokinetics of first semaglutid drug in Russian Federation: results of open-label randomized clinical trial. Medical Council. 2023;(16):77–82. DOI: 10.21518/ms2023-312. RussianZhang X., Belousoff M.J., Zhao P., Kooistra A.J., Truong T.T., Ang S.Y., Underwood C.R., Egebjerg T., Šenel P., Stewart G.D., Liang Y.L., Glukhova A., Venugopal H., Christopoulos A., Furness S.G.B., Miller L.J., Reedtz-Runge S., Langmead C.J., Gloriam D.E., Danev R., Sexton P.M., Wootten D. Differential GLP-1R Binding and Activation by Peptide and Non-peptide Agonists // Mol Cell. – 2020. – Vol. 80, No. 3. – P. 485–500.e7. DOI: 10.1016/j.molcel.2020.09.020Zhang X, Belousoff MJ, Zhao P, Kooistra AJ, Truong TT, Ang SY, Underwood CR, Egebjerg T, Šenel P, Stewart GD, Liang YL, Glukhova A, Venugopal H, Christopoulos A, Furness SGB, Miller LJ, Reedtz-Runge S, Langmead CJ, Gloriam DE, Danev R, Sexton PM, Wootten D. Differential GLP-1R binding and activation by peptide and non-peptide agonists. Mol Cell. 2020;80(3):485–500.e7. DOI: 10.1016/j.molcel.2020.09.020Zhao P., Liang Y.L., Belousoff M.J., Deganutti G., Fletcher M.M., Willard F.S., Bell M.G., Christe M.E., Sloop K.W., Inoue A., Truong T.T., Clydesdale L., Furness S.G.B., Christopoulos A., Wang M.W., Miller L.J., Reynolds C.A., Danev R., Sexton P.M., Wootten D. Activation of the GLP-1 receptor by a non-peptidic agonist // Nature. – 2020. – Vol. 577, No. 7790. – P. 432–436. DOI: 10.1038/s41586-019-1902-zZhao P, Liang YL, Belousoff MJ, Deganutti G, Fletcher MM, Willard FS, Bell MG, Christe ME, Sloop KW, Inoue A, Truong TT, Clydesdale L, Furness SGB, Christopoulos A, Wang MW, Miller LJ, Reynolds CA, Danev R, Sexton PM, Wootten D. Activation of the GLP-1 receptor by a non-peptidic agonist. Nature. 2020;577(7790):432–6. DOI: 10.1038/s41586-019-1902-zFreeman J.L.R., Dunn I.M., Valcarce C. Beyond topline results for the oral (non-peptide) GLP-1R agonist TTP273 in type 2 diabetes: how much and when // Diabetol. Conf. 53rd Annu. Meet. Eur. Assoc. study diabetes, EASD 2017. Port. – 2017. – Vol. 60. – P. S51-S52.Freeman JLR, Dunn IM, Valcarce C. Beyond topline results for the oral (non-peptide) GLP-1R agonist TTP273 in type 2 diabetes: how much and when. Diabetol. Conf. 53rd Annu. Meet. Eur. Assoc. study diabetes, EASD 2017. Port. 2017;60:S51-S52.Girdhar K., Thakur S., Gaur P., Choubey A., Dogra S., Dehury B., Kumar S., Biswas B., Dwivedi D.K., Ghosh S., Mondal P. Design, synthesis, and biological evaluation of a small molecule oral agonist of the glucagon-like-peptide-1 receptor // J Biol Chem. – 2022. – Vol. 298, No. 5. – P. 101889. DOI: 10.1016/j.jbc.2022.101889Girdhar K, Thakur S, Gaur P, Choubey A, Dogra S, Dehury B, Kumar S, Biswas B, Dwivedi DK, Ghosh S, Mondal P. Design, synthesis, and biological evaluation of a small molecule oral agonist of the glucagon-like-peptide-1 receptor. J Biol Chem. 2022;298(5):101889. DOI: 10.1016/j.jbc.2022.101889Karakasis P., Patoulias D., Pamporis K., Stachteas P., Bougioukas K.I., Klisic A., Fragakis N., Rizzo M. Safety and efficacy of the new, oral, small-molecule, GLP-1 receptor agonists orforglipron and danuglipron for the treatment of type 2 diabetes and obesity: systematic review and meta-analysis of randomized controlled trials // Metabolism. – 2023. – Vol. 149. – P. 155710. DOI: 10.1016/j.metabol.2023.155710Karakasis P, Patoulias D, Pamporis K, Stachteas P, Bougioukas K.I, Klisic A, Fragakis N, Rizzo M. Safety and efficacy of the new, oral, small-molecule, GLP-1 receptor agonists orforglipron and danuglipron for the treatment of type 2 diabetes and obesity: systematic review and meta-analysis of randomized controlled trials. Metabolism. 2023;149:155710. DOI: 10.1016/j.metabol.2023.155710Bueno A.B., Sun B., Willard F.S., Feng D., Ho J.D., Wainscott D.B., Showalter A.D., Vieth M., Chen Q., Stutsman C., Chau B., Ficorilli J., Agejas F.J., Cumming G.R., Jiménez A., Rojo I., Kobilka T.S., Kobilka B.K., Sloop K.W. Structural insights into probe-dependent positive allosterism of the GLP-1 receptor // Nat Chem Biol. – 2020. – Vol. 16, No. 10. – P. 1105–1110. DOI: 10.1038/s41589-020-0589-7Bueno AB, Sun B, Willard FS, Feng D, Ho JD, Wainscott DB, Showalter AD, Vieth M, Chen Q, Stutsman C, Chau B, Ficorilli J, Agejas FJ, Cumming GR, Jiménez A, Rojo I, Kobilka TS, Kobilka BK, Sloop KW. Structural insights into probe-dependent positive allosterism of the GLP-1 receptor. Nat Chem Biol. 2020;16(10):1105–10. DOI: 10.1038/s41589-020-0589-7King K., Lin N.P., Cheng Y.H., Chen G.H., Chein R.J. Isolation of Positive Modulator of Glucagon-like Peptide-1 Signaling from Trigonella foenum-graecum (Fenugreek) Seed // J Biol Chem. – 2015. – Vol. 290, No. 43. – P. 26235–26248. DOI: 10.1074/jbc.M115.672097King K, Lin NP, Cheng YH, Chen GH, Chein RJ. Isolation of Positive Modulator of Glucagon-like Peptide-1 Signaling from Trigonella foenum-graecum (Fenugreek) Seed. J Biol Chem. 2015;290(43):26235–48. DOI: 10.1074/jbc.M115.672097Huthmacher J.A., Meier J.J., Nauck M.A. Efficacy and Safety of Short- and Long-Acting Glucagon-Like Peptide 1 Receptor Agonists on a Background of Basal Insulin in Type 2 Diabetes: A Meta-analysis // Diabetes Care. – 2020. – Vol. 43, No. 9. – P. 2303–2312. DOI: 10.2337/dc20-0498Huthmacher JA, Meier JJ, Nauck MA. Efficacy and safety of short- and long-acting glucagon-like peptide 1 receptor agonists on a background of basal insulin in type 2 diabetes: a meta-analysis. Diabetes Care. 2020;43(9):2303–12. DOI: 10.2337/dc20-0498Baggio L.L., Drucker D.J. Glucagon-like peptide-1 receptor co-agonists for treating metabolic disease // Mol Metab. – 2021. – Vol. 46. – P. 101090. DOI: 10.1016/j.molmet.2020.101090Baggio LL, Drucker DJ. Glucagon-like peptide-1 receptor co-agonists for treating metabolic disease. Mol Metab. 2021;46:101090. DOI: 10.1016/j.molmet.2020.101090Finan B., Yang B., Ottaway N., Smiley D.L., Ma T., Clemmensen C., Chabenne J., Zhang L., Habegger K.M., Fischer K., Campbell J.E., Sandoval D., Seeley R.J., Bleicher K., Uhles S., Riboulet W., Funk J., Hertel C., Belli S., Sebokova E., Conde-Knape K., Konkar A., Drucker D.J., Gelfanov V., Pfluger P.T., Müller T.D., Perez-Tilve D., DiMarchi R.D., Tschöp M.H. A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents // Nat Med. – 2015. – Vol. 21, No. 1. – P. 27–36. DOI: 10.1038/nm.3761Finan B, Yang B, Ottaway N, Smiley DL, Ma T, Clemmensen C, Chabenne J, Zhang L, Habegger KM, Fischer K, Campbell JE, Sandoval D, Seeley RJ, Bleicher K, Uhles S, Riboulet W, Funk J, Hertel C, Belli S, Sebokova E, Conde-Knape K, Konkar A, Drucker DJ, Gelfanov V, Pfluger PT, Müller TD, Perez-Tilve D, DiMarchi RD, Tschöp MH. A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents. Nat Med. 2015;21(1):27–36. DOI: 10.1038/nm.3761Finan B., Ma T., Ottaway N., Müller T.D., Habegger K.M., Heppner K.M., Kirchner H., Holland J., Hembree J., Raver C., Lockie S.H., Smiley D.L., Gelfanov V., Yang B., Hofmann S., Bruemmer D., Drucker D.J., Pfluger P.T., Perez-Tilve D., Gidda J., Vignati L., Zhang L., Hauptman J.B., Lau M., Brecheisen M., Uhles S., Riboulet W., Hainaut E., Sebokova E., Conde-Knape K., Konkar A., DiMarchi R.D., Tschöp M.H. Unimolecular dual incretins maximize metabolic benefits in rodents, monkeys, and humans // Sci Transl Med. – 2013. – Vol. 5, No. 209. – P. 209ra151. DOI: 10.1126/scitranslmed.3007218Finan B, Ma T, Ottaway N, Müller TD, Habegger KM, Heppner KM, Kirchner H, Holland J, Hembree J, Raver C, Lockie SH, Smiley DL, Gelfanov V, Yang B, Hofmann S, Bruemmer D, Drucker DJ, Pfluger PT, Perez-Tilve D, Gidda J, Vignati L, Zhang L, Hauptman JB, Lau M, Brecheisen M, Uhles S, Riboulet W, Hainaut E, Sebokova E, Conde-Knape K, Konkar A, DiMarchi RD, Tschöp MH. Unimolecular dual incretins maximize metabolic benefits in rodents, monkeys, and humans. Sci. Transl. Med. 2013;5(209):209ra151. DOI: 10.1126/scitranslmed.3007218Bech E.M., Voldum-Clausen K., Pedersen S.L., Fabricius K., Rudkjær L.C.B., Hansen H.H., Jelsing J. Adrenomedullin and glucagon-like peptide-1 have additive effects on food intake in mice // Biomed Pharmacother. – 2019. – Vol. 109. – P. 167–173. DOI: 10.1016/j.biopha.2018.10.040Bech EM, Voldum-Clausen K, Pedersen SL, Fabricius K, Rudkjær LCB, Hansen HH, Jelsing J. Adrenomedullin and glucagon-like peptide-1 have additive effects on food intake in mice. Biomed Pharmacother. 2019;109:167–73. DOI: 10.1016/j.biopha.2018.10.040Decara J., Rivera P., Arrabal S., Vargas A., Serrano A., Pavón F.J., Dieguez C., Nogueiras R., Rodríguez de Fonseca F., Suárez J. Cooperative role of the glucagon-like peptide-1 receptor and β3-adrenergic-mediated signalling on fat mass reduction through the downregulation of PKA/AKT/AMPK signalling in the adipose tissue and muscle of rats // Acta Physiol (Oxf). – 2018. – Vol. 222, No. 4. – P. e13008. DOI: 10.1111/apha.13008Decara J, Rivera P, Arrabal S, Vargas A, Serrano A, Pavón FJ, Dieguez C, Nogueiras R, Rodríguez de Fonseca F, Suárez J. Cooperative role of the glucagon-like peptide-1 receptor and β3-adrenergic-mediated signalling on fat mass reduction through the downregulation of PKA/AKT/AMPK signalling in the adipose tissue and muscle of rats. Acta Physiol. (Oxf.). 2018;222(4):e13008. DOI: 10.1111/apha.13008Bojanowska E., Radziszewska E. Combined stimulation of glucagon-like peptide-1 receptor and inhibition of cannabinoid CB1 receptor act synergistically to reduce food intake and body weight in the rat // J Physiol Pharmacol. – 2011. – Vol. 62, No. 4. – P. 395–402.Bojanowska E, Radziszewska E. Combined stimulation of glucagon-like peptide-1 receptor and inhibition of cannabinoid CB1 receptor act synergistically to reduce food intake and body weight in the rat. J Physiol Pharmacol. 2011;62(4):395–402.Jouihan H., Will S., Guionaud S., Boland M.L., Oldham S., Ravn P., Celeste A., Trevaskis J.L. Superior reductions in hepatic steatosis and fibrosis with co-administration of a glucagon-like peptide-1 receptor agonist and obeticholic acid in mice // Mol Metab. – 2017. – Vol. 6, No. 11. – P. 1360–1370. DOI: 10.1016/j.molmet.2017.09.001Jouihan H, Will S, Guionaud S, Boland ML, Oldham S, Ravn P, Celeste A, Trevaskis JL. Superior reductions in hepatic steatosis and fibrosis with co-administration of a glucagon-like peptide-1 receptor agonist and obeticholic acid in mice. Mol Metab. 2017;6(11):1360–70. DOI: 10.1016/j.molmet.2017.09.001Elvert R., Bossart M., Herling A.W., Weiss T., Zhang B., Kannt A., Wagner M., Haack T., Evers A., Dudda A., Keil S., Lorenz M., Lorenz K., Riz M., Hennerici W., Larsen P.J. Team players or opponents: coadministration of selective glucagon and GLP-1 receptor agonists in obese diabetic monkeys // Endocrinology. – 2018. – Vol. 159, No. 8. – P. 3105–3119. DOI: 10.1210/en.2018-00399Elvert R, Bossart M, Herling AW, Weiss T, Zhang B, Kannt A, Wagner M, Haack T, Evers A, Dudda A, Keil S, Lorenz M, Lorenz K, Riz M, Hennerici W, Larsen PJ. Team players or opponents: coadministration of selective glucagon and GLP-1 receptor agonists in obese diabetic monkeys. Endocrinology. 2018;159(8):3105–19. DOI: 10.1210/en.2018-00399Дружилов М. А., Кузнецова Т. Ю., Чумакова Г. А. Мульти-агонисты «инкретиновой оси» как перспективный инструмент управления кардиометаболическим риском при синдроме висцерального ожирения // Российский кардиологический журнал. – 2022. – Т. 27, № 4. – C. 4755. DOI: 10.15829/1560-4071-2022-4755Druzhilov MA, Kuznetsova TYu, Chumakova GA. Multiagonists of the “incretin axis” as a promising tool for managing cardiometabolic risk in visceral obesity. Russian Journal of Cardiology. 2022;27(4):4755. DOI: 10.15829/1560-4071-2022-4755. RussianSimonsen L., Lau J., Kruse T., Guo T., McGuire J., Jeppesen J.F., Niss K., Sauerberg P., Raun K., Dornonville de la Cour C. Preclinical evaluation of a protracted GLP-1/glucagon receptor co-agonist: Translational difficulties and pitfalls // PLoS One. – 2022. – Vol. 17, No. 3. – P. e0264974. DOI: 10.1371/journal.pone.0264974Simonsen L, Lau J, Kruse T, Guo T, McGuire J, Jeppesen JF, Niss K, Sauerberg P, Raun K, Dornonville de la Cour C. Preclinical evaluation of a protracted GLP-1/glucagon receptor co-agonist: Translational difficulties and pitfalls. PLoS One. 2022;17(3):e0264974. DOI: 10.1371/journal.pone.0264974van Witteloostuijn S.B., Dalbøge L.S., Hansen G., Midtgaard S.R., Jensen G.V., Jensen K.J., Vrang N., Jelsing J., Pedersen S.L. GUB06-046, a novel secretin/glucagon-like peptide 1 co-agonist, decreases food intake, improves glycemic control, and preserves beta cell mass in diabetic mice // J Pept Sci. – 2017. – Vol. 23, No. 12. – P. 845–854. DOI: 10.1002/psc.3048van Witteloostuijn SB, Dalbøge LS, Hansen G, Midtgaard SR, Jensen GV, Jensen KJ, Vrang N, Jelsing J, Pedersen SL. GUB06-046, a novel secretin/glucagon-like peptide 1 co-agonist, decreases food intake, improves glycemic control, and preserves beta cell mass in diabetic mice. J Pept Sci. 2017;23(12):845–54. DOI: 10.1002/psc.3048Stensen S., Gasbjerg L.S., Helsted M.M., Hartmann B., Christensen M.B., Knop F.K. GIP and the gut-bone axis – Physiological, pathophysiological and potential therapeutic implications // Peptides. – 2020. – Vol. 125. – P. 170197. DOI: 10.1016/j.peptides.2019.170197Stensen S, Gasbjerg LS, Helsted MM, Hartmann B, Christensen MB, Knop FK. GIP and the gut-bone axis – Physiological, pathophysiological and potential therapeutic implications. Peptides. 2020;125:170197. DOI: 10.1016/j.peptides.2019.170197Del Prato S., Kahn S.E., Pavo I., Weerakkody G.J., Yang Z., Doupis J., Aizenberg D., Wynne A.G., Riesmeyer J.S., Heine R.J., Wiese R.J.; SURPASS-4 Investigators. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial // Lancet. – 2021. – Vol. 398, No. 10313. – P. 1811–1824. DOI: 10.1016/S0140-6736(21)02188-7Del Prato S, Kahn SE, Pavo I, Weerakkody GJ, Yang Z, Doupis J, Aizenberg D, Wynne AG, Riesmeyer JS, Heine RJ, Wiese RJ; SURPASS-4 Investigators. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet. 2021;398(10313):1811–24. DOI: 10.1016/S0140-6736(21)02188-7Jastreboff A.M., Kaplan L.M., Frías J.P., Wu Q., Du Y., Gurbuz S., Coskun T., Haupt A., Milicevic Z., Hartman M.L.; Retatrutide Phase 2 Obesity Trial Investigators. Triple-Hormone-Receptor Agonist Retatrutide for Obesity – A Phase 2 Trial // N Engl J Med. – 2023. – Vol. 389, No. 6. – P. 514-526. DOI: 10.1056/NEJMoa2301972Jastreboff AM, Kaplan LM, Frías JP, Wu Q, Du Y, Gurbuz S, Coskun T, Haupt A, Milicevic Z, Hartman ML; Retatrutide Phase 2 Obesity Trial Investigators. Triple-Hormone-Receptor Agonist Retatrutide for Obesity – A Phase 2 Trial. N Engl J Med. 2023;389(6):514-26. DOI: 10.1056/NEJMoa2301972Fosgerau K., Jessen L., Lind Tolborg J., Østerlund T., Schæffer Larsen K., Rolsted K., Brorson M., Jelsing J., Skovlund Ryge Neerup T. The novel GLP-1-gastrin dual agonist, ZP3022, increases β-cell mass and prevents diabetes in db/db mice // Diabetes Obes Metab. – 2013. – Vol. 15, No. 1. – P. 62–71. DOI: 10.1111/j.1463-1326.2012.01676.xFosgerau K, Jessen L, Lind Tolborg J, Østerlund T, Schæffer Larsen K, Rolsted K, Brorson M, Jelsing J, Skovlund Ryge Neerup T. The novel GLP-1-gastrin dual agonist, ZP3022, increases β-cell mass and prevents diabetes in db/db mice. Diabetes Obes Metab. 2013;15(1):62–71. DOI: 10.1111/j.1463-1326.2012.01676.xChodorge M., Celeste A.J., Grimsby J., Konkar A., Davidsson P., Fairman D., Jenkinson L., Naylor J., White N., Seaman J.C., Dickson K., Kemp B., Spooner J., Rossy E., Hornigold D.C., Trevaskis J.L., Bond N.J., London T.B., Buchanan A., Vaughan T., Rondinone C.M., Osbourn J.K. Engineering of a GLP-1 analogue peptide/anti-PCSK9 antibody fusion for type 2 diabetes treatment // Sci Rep. – 2018. – Vol. 8, No. 1. – P. 17545. DOI: 10.1038/s41598-018-35869-4Chodorge M, Celeste AJ, Grimsby J, Konkar A, Davidsson P, Fairman D, Jenkinson L, Naylor J, White N, Seaman JC, Dickson K, Kemp B, Spooner J, Rossy E, Hornigold DC, Trevaskis JL, Bond NJ, London TB, Buchanan A, Vaughan T, Rondinone CM, Osbourn JK. Engineering of a GLP-1 analogue peptide/anti-PCSK9 antibody fusion for type 2 diabetes treatment. Sci Rep. 2018;8(1):17545. DOI: 10.1038/s41598-018-35869-4Jain M., Carlson G., Cook W., Morrow L., Petrone M., White N.E., Wang T., Naylor J., Ambery P., Lee C., Hirshberg B. Randomised, phase 1, dose-finding study of MEDI4166, a PCSK9 antibody and GLP-1 analogue fusion molecule, in overweight or obese patients with type 2 diabetes mellitus // Diabetologia. – 2019. – Vol. 62, No. 3. – P. 373–386. DOI: 10.1007/s00125-018-4789-6Jain M, Carlson G, Cook W, Morrow L, Petrone M, White NE, Wang T, Naylor J, Ambery P, Lee C, Hirshberg B. Randomised, phase 1, dose-finding study of MEDI4166, a PCSK9 antibody and GLP-1 analogue fusion molecule, in overweight or obese patients with type 2 diabetes mellitus. Diabetologia. 2019;62(3):373–86. DOI: 10.1007/s00125-018-4789-6

The authors declare that there are no conflicts of interest present.