pmedpharmФармация и фармакологияPharmacy & Pharmacology2307-92662413-2241Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical Univer10.19163/2307-9266-2023-11-1-19-47pmedpharm-1257Research ArticleОБЗОРЫ, ЛЕКЦИИREVIEWS, LECTURESФизиология, фармакология и перспективы применения ингибиторов дипептидилпептидазы-4Physiology, pharmacology and prospects for dipeptidilpeptidase-4 inhibitors usehttps://orcid.org/0000-0002-1116-3425КуркинД. В.KurkinD. V.

доктор фармацевтических наук, доцент, профессор кафедры клинической фармакологии и интенсивной терапии ФГБОУ ВО ВолгГМУ Минздрава России

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

Doctor of Sciences (Pharmacy), Associate Professor, Professor of the Department of Clinical Pharmacology and Intensive Care, Volgograd State Medical University

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

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

кандидат медицинских наук, старший научный сотрудник лаборатории фармакологии сердечно-сосудистых средств НЦИЛС ФГБОУ ВО ВолгГМУ Минздрава России

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

Candidate of Sciences (Medicine), Senior Researcher, Laboratory of Pharmacology of Cardiovascular Drugs, Volgograd State Medical University

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

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), Associate Professor, Head of the Laboratory of Neuropsychopharmacology, Volgograd State Medical University

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

e.i.morkovin@gmail.comhttps://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), Associate Professor, Deputy Director of Research Center for Innovative Medicines, Volgograd State Medical University

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

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

кандидат медицинских наук, доцент кафедры клинической фармакологии и интенсивной терапии ФГБОУ ВО ВолгГМУ Минздрава России

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

Candidate of Sciences (Medicine), Associate Professor, Department of Clinical Pharmacology and Intensive Care, Volgograd State Medical University

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

yvgorbunova@yandex.ruhttps://orcid.org/0000-0003-3916-7249ВолотоваЕ. В.VolotovaE. V.

доктор медицинских наук, профессор, институт НМФО ФГБОУ ВО ВолгГМУ Минздрава России

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

Doctor of Sciences (Medicine), Professor, Continuing Medical and Pharmaceutical Education Institute, Volgograd State Medical University

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

a-zlato@mail.ruhttps://orcid.org/0000-0003-2308-0608МакаренкоИ. Е.MakarenkoI. E.

кандидат медицинских наук, руководитель медицинского департамента, ЗАО «Фарм-Холдинг»; научный сотрудник ФГБОУ ВО МГМСУ им. А.И. Евдокимова Минздрава России

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

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

Candidate of Sciences (Medicine), Head of the Medical Department of Farm-Holding; researcher of Moscow State Medical and Dental University n. a. A.I. Evdokimov.

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

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

 

Igor.Makarenko@geropharm.comhttps://orcid.org/0000-0002-8445-1129СапароваВ. Б.SaparovaV. B.

руководитель лаборатории фармакологии, ЗАО «Фарм-Холдинг»; научный сотрудник ФГБОУ ВО МГМСУ им. А.И. Евдокимова Минздрава России

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

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

Head of the Laboratory of Pharmacology, Farm-Holding; researcher of Moscow State Medical and Dental University n. a. A.I. Evdokimov.

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

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

 

Valeriya.Saparova@geropharm.comhttps://orcid.org/0000-0003-4594-6097ДрайР. В.DraiR. V.

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

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

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

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

roman.drai@geropharm.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; директор НЦИЛС ВолгГМУ, 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, Director of Research Center for Innovative Medicines, Volgograd 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.ruФедеральное государственное бюджетное образовательное учреждение высшего образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияVolgograd State Medical UniversityRussian Federation1. Закрытое акционерное общество «Фарм-Холдинг» 2. Федеральное государственное бюджетное образовательное учреждение высшего образования «Московский государственный медико-стоматологический университет имени А.И. Евдокимова» Министерства здравоохранения Российской ФедерацииРоссия1. Moscow State Medical and Dental University named after A.I. Evdokimov 2. Farm-Holding,Russian FederationЗакрытое акционерное общество «Фарм-Холдинг»РоссияFarm-HoldingRussian Federation2023280420231111947Copyright © Куркин Д.В., Бакулин Д.А., Морковин Е.И., Стрыгин А.В., Горбунова Ю.В., Волотова Е.В., Макаренко И.Е., Сапарова В.Б., Драй Р.В., Петров В.И., 20232023Куркин Д.В., Бакулин Д.А., Морковин Е.И., Стрыгин А.В., Горбунова Ю.В., Волотова Е.В., Макаренко И.Е., Сапарова В.Б., Драй Р.В., Петров В.И.Kurkin D.V., Bakulin D.A., Morkovin E.I., Strygin A.V., Gorbunova Y.V., Volotova E.V., Makarenko I.E., Saparova V.B., Drai R.V., Petrov V.I.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/1257

Современные требования к терапии сахарного диабета 2 типа (СД 2) включают не только достижение гликемического контроля, но и снижение риска развития сердечно-сосудистых осложнений. Ингибиторы дипептидилпептидазы 4 (ДПП-4) уступают по эффективности некоторым другим активно развивающимся группам гипогликемических препаратов (ингибиторы SGLT2 и агонисты рецепторов ГПП-1), однако представляются актуальными и в настоящее время.

Цель

Цель. Проанализировать данные литературы о терапевтическом потенциале и результатах исследований ингибиторов ДПП-4.

Материалы и методы

Материалы и методы. При поиске материала для написания обзорной статьи использовали реферативные базы PubMed, Google Scholar и e-Library. Поиск осуществлялся по публикациям за период с 2006 по 2022 год, с использованием следующих ключевых слов: ингибиторы ДПП-4; глюкагоноподобный пептид-1 (ГПП-1); глюкозозависимый инсулинотропный пептид (ГИП); ситаглиптин и другие препараты.

Результаты

Результаты. ДПП-4 принадлежит к семейству сериновых протеаз и участвует в деградации некоторого количества хемокинов и пептидных гормонов, в том числе и инкретинов, секретируемых L- и K-клетками кишечника: ГПП-1 и ГИП, которые регулируют постпрандиальную секрецию инсулина и функцию β-клеток, модулируют тощаковую и постпрандиальную секрецию глюкагона, регулируют пищевое поведение и оказывают множество плейотропных эффектов (иммуномодулирующее, противовоспалительное, антифибротическое действие и др.). Ингибиторы ДПП-4 снижают активность фермента на 70–90%, повышая уровень инкретинов в плазме в 2–4 раза и применяются для лечения СД 2 с 2006 года. Сейчас на рынке разных стран присутствуют 13 ингибиторов ДПП-4, различающихся прежде всего фармакокинетическими параметрами. Они активно используются в комбинированной терапии СД 2, повышая эффективность гликемического контроля без увеличения риска развития гипогликемии. Появляются данные о терапевтическом потенциале ингибиторов ДПП-4 при COVID-19.

Заключение

Заключение. Пероральная форма, возможность создавать эффективные комбинации с другими гипогликемическими препаратами без увеличения риска гипогликемии, плейотропные эффекты ингибиторов ДПП-4 делают данную группу актуальной и в настоящее время.

Modern requirements for the treatment of type 2 diabetes mellitus (DM2) include not only achieving a glycemic control, but also reducing the risk of developing cardiovascular complications. Dipeptidyl peptidase 4 (DPP-4) inhibitors are inferior in the effectiveness to some other actively developing groups of hypoglycemic drugs (SGLT2 inhibitors and GLP-1 receptor agonists); however, they seem relevant at the present time.

The aim of the study is to analyze the literature data on the therapeutic potential and results of the of DPP-4 inhibitors research.

Materials and methods

Materials and methods. When searching for the review article materials, the abstracting databases of PubMed, Google Scholar and e-Library were used. The search was carried out on the publications for the period from 2006 to 2022, using the following keywords: DPP-4 inhibitors; glucagonlike peptide-1 (GLP-1); glucose-dependent insulinotropic peptide (GIP); sitagliptin, and other drugs.

Results

Results. DPP-4 belongs to the serine proteases family and is involved in the degradation of various chemokines and peptide hormones, including incretins secreted by intestinal L- and K-cells – GLP-1 and GIP. They regulate a postprandial insulin secretion and a β-cell function, modulate a fasting and postprandial glucagon secretion, regulate the eating behavior and have many pleiotropic (immunomodulatory, anti-inflammatory, antifibrotic, etc.) effects. DPP-4 inhibitors reduce an enzyme activity by 70–90%, increasing plasma incretin levels by 2–4 times and have been used to treat DM2 since 2006. Now there are 13 DPP-4 inhibitors on the market in different countries, differing primarily in pharmacokinetic parameters. They are actively used in the combination therapy for type 2 diabetes, increasing the glycemic control effectiveness without increasing the risk of hypoglycemia. The evidence is emerging about the therapeutic potential of DPP-4 inhibitors in COVID-19.

Conclusion

Conclusion. A peroral form, an ability to create effective combinations with other hypoglycemic drugs without increasing the risk of hypoglycemia, the pleiotropic effects of DPP-4 inhibitors, make this group relevant at the present time.

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