pmedpharmФармация и фармакологияPharmacy & Pharmacology2307-92662413-2241Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical Univer10.19163/2307-9266-2023-11-4-324-346pmedpharm-1385Research ArticleОРИГИНАЛЬНАЯ СТАТЬЯRESEARCH ARTICLEСравнительный анализ физико-химических свойств, биоэквивалентности, безопасности и переносимости отечественного семаглутидаComparative analysis of physicochemical properties, bioequivalence, safety and tolerability of the first domestic semaglutidehttps://orcid.org/0000-0002-7936-7619АметовА. С.AmetovA. S.

доктор медицинских наук, профессор, заведующий кафедрой эндокринологии, заведующий сетевой кафедрой ЮНЕСКО по теме «Биоэтика сахарного диабета как глобальная проблема», ФГБОУ ДПО РМАНПО Минздрава России; заслуженный деятель науки РФ.

125993, Россия, г. Москва, ул. Баррикадная, д. 2/1, стр. 1

Doctor of Sciences (Medicine), Professor, Head of the Department of Endocrinology, Head of the UNESCO Network Department on the topic “Bioethics of Diabetes Mellitus as a Global Problem”, Russian Medical Academy of Continuing Professional Education; Honored Scientist of the Russian Federation.

Bld. 1, 2/1, Barrikadnaya Str., Moscow, Russia, 125993

 

alexander.ametov@gmail.comhttps://orcid.org/0000-0002-1185-8630ШохинИ. Е.ShokhinI. E.

доктор фармацевтических наук, генеральный директор ООО «Центр Фармацевтической Аналитики», Москва, Россия. 

117638, Россия, г. Москва, Симферопольский бульвар, д. 8

Doctor of Sciences (Pharmacy), General Director of Center for Pharmaceutical Analytics LLC, Moscow, Russia.

8, Simferopolsky Blvd, Moscow, Russia, 117638

i.shohin@cpha.ruhttps://orcid.org/0000-0002-3325-2605РогожинаЕ. А.RogozhinaE. A.

соискатель кафедры биотехнологии и промышленной фармации, ФГБОУ ВО «МИРЭА – Российский технологический университет». 

119454, Россия, г. Москва, пр-кт Вернадского, д. 78

applicant for the Department of Biotechnology and Industrial Pharmacy of MIREA – Russian Technological University.

78, Vernadsky Ave., Moscow, Russia, 119454.

e.kate.rogozhina@gmail.comhttps://orcid.org/0009-0001-0881-4880БодроваТ. Г.BodrovaT. G.

соискатель научно-образовательного института фармации им. К.М. Лакина ФГБОУ ВО МГМСУ им. А.И. Евдокимова Минздрава России. 

127006, Россия, г. Москва, ул. Долгоруковская, д. 4

applicant of the Scientific and Educational Institute of Pharmacy n.a. K.M. Lakin of Yevdokimov Moscow State Medical and Dental University. 

4, Dolgorukovskaya Str., Moscow, Russia, 127006

btatg@mail.ruhttps://orcid.org/0000-0003-3008-4594НевретдиноваМ. Е.NevretdinovaM. E.

врач-терапевт ООО «Практика здоровья».

117624, Россия, г. Москва, ул. Скобелевская, д. 1

therapist of Health Practice LLC, Moscow, Russia.

1, Skobelevskaya Str., Moscow, Russia, 117624

mariamdoc@mail.ruhttps://orcid.org/0000-0001-5998-4874БелыйП. А.BelyP. A.

кандидат медицинских наук, старший лаборант кафедры пропедевтики внутренних болезней и гастроэнтерологии ФГБОУ ВО МГМСУ им. А.И. Евдокимова Минздрава России. 

127006, Россия, г. Москва, ул. Долгоруковская, д. 4

Candidate of Sciences (Medicine), senior laboratory assistant at the Department of Propaedeutics of Internal Diseases and Gastroenterology of Yevdokimov Moscow State Medical and Dental University.

4, Dolgorukovskaya Str., Moscow, Russia, 127006

pbely@ncpharm.ruhttps://orcid.org/0000-0002-7348-9412ЗаславскаяК. Я.ZaslavskayaK. Ya.

ассистент кафедры биологической и фармацевтической химии с курсом организации и управления фармацией Медицинский институт ФГБОУ ВО «МГУ им. Н.П. Огарева». 

430005, Россия, г. Саранск, ул. Большевистская, д. 68

assistant of the Department of BIological and Pharmaceutical Chemistry with a Course Organization and Management of Pharmacy, Medical Institute of National Research Ogarev Mordovia State University. 

68, Bolshevistskaya Str., Saransk, Russia, 430005

kiryonok@yandex.ruhttps://orcid.org/0000-0002-7251-8744ЩербаковаВ. С.ScherbakovaV. S.

кандидат биологических наук, ассистент кафедры фармакологии ФГБОУ ВО Тверского ГМУ Минздрава России. 

170100, Россия, г. Тверь, ул. Советская, д. 4

Candidate of Sciences (Biology), Assistant Professor, Department of Pharmacology, Tver State Medical University.

4, Sovetskaya Str., Tver, Russia, 170100

Victoria_kaptar@mail.ruhttps://orcid.org/0000-0002-1116-3425КуркинД. В.KurkinD. V.

доктор фармацевтических наук, доцент, директор научно-образовательного института фармации им. К.М. Лакина ФГБОУ ВО МГМСУ им. А.И. Евдокимова Минздрава России. 

127006, Россия, г. Москва, ул. Долгоруковская, д. 4

 

Doctor of Sciences (Pharmacy), Associate Professor, Director of the Scientific and Educational Institute of Pharmacy n.a. K.M. Lakin Yevdokimov Moscow State Medical and Dental University. 

4, Dolgorukovskaya Str., Moscow, Russia, 127006

strannik986@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/0000-0001-7778-8391МищенкоЕ. С.MishchenkoE. S.

кандидат фармацевтических наук, старший преподаватель кафедры токсикологической и аналитической химии ПМФИ – филиала ФГБОУ ВО ВолгГМУ Минздрава России. 

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

Candidate of Sciences (Pharmacy), Senior Teacher of the Department of Toxicological and Analytical Chemistry, Pyatigorsk Medical and Pharmaceutical Institute – branch of Volgograd State Medical University. 

11, Kalinin Ave., Pyatigorsk, Russia, 357532

ekaterina-mischenko1809@mail.ruhttps://orcid.org/0009-0005-0553-8365КесоваЭ. Ю.KesovaE. Yu.

студентка 6-го курса Института клинической медицины им. Н.В. Склифосовского, ФГАОУ ВО Первый МГМУ им. И.М. Сеченова Минздрава России (Сеченовский университет).

119991, Россия, г. Москва, ул. Трубецкая, д. 8, стр. 2

6th year student of the Institute of Clinical Medicine n.a. N.V. Sklifosovsky, Sechenov First Moscow State Medical University (Sechenov University). 

Bldg. 2, 8, Trubetskaya Str., Moscow, Russia, 119991

elkesova@icloud.comhttps://orcid.org/0000-0001-8373-6109КозловЕ. Д.KozlovE. D.

старший преподаватель кафедры амбулаторно-поликлинической терапии медицинского института, ФГБОУ ВО «МГУ им. Н.П. Огарева». 

430005, Россия, г. Саранск, ул. Большевистская, д. 68

senior lecturer of the department of outpatient therapy of the medical institute of National Research Ogarev Mordovia State University. 

68, Bolshevistskaya Str., Saransk, Russia, 430005

dr.kozlov@yandex.ruhttps://orcid.org/0000-0002-8192-7902СамошкинаЕ. С.SamoshkinaE. S.

кандидат медицинских наук, доцент кафедры педиатрии ФГБОУ ВО «МГУ им. Н.П. Огарева».

430005, Россия, г. Саранск, ул. Большевистская, д. 68

Candidate of Sciences (Medicine), assistant professor of National Research Ogarev Mordovia State University.

68, Bolshevistskaya Str., Saransk, Russia, 430005

esamoshkina@yandex.ruhttps://orcid.org/0000-0002-4007-7112АндреевД. Н.AndreevD. N.

кандидат медицинских наук, доцент, доцент кафедры пропедевтики внутренних болезней и гастроэнтерологии ФГБОУ ВО «Российский университет медицины» Минздрава РФ.

127994, Россия, ГСП-4, г. Москва, Рахмановский пер, д. 3.

Candidate of Medical Sciences, Associate Professor, Associate Professor of the Department of Propaedeutics of Internal Diseases and Gastroenterology of the Russian University of Medicine of the Ministry of Health of the Russian Federation.

3, Rakhmanovsky Ln., Moscow, GSP-4, Russia, 127994

dna-mit8@mail.ruhttps://orcid.org/0000-0003-0826-4177КазаишвилиЮ. Г.KazaishviliYu. G.

кандидат биологических наук, старший научный сотрудник научно-исследовательской лаборатории ФГБОУ ВО Тверского ГМУ Минздрава РФ. 

170100, Россия, г. Тверь, ул. Советская, д. 4

Candidate Sciences (Biology), assistant at the Department of Pharmacology of the Tver State Medical University.

4, Sovetskaya Str., Tver, Russia, 170100

ykaza@bk.ruhttps://orcid.org/0000-0003-3456-9409НосковС. М.NoskovS. M.

доктор медицинских наук, профессор, заведующий кафедрой госпитальной терапии ФГБОУ ВО ЯГМУ Минздрава России; терапевт, главный исследователь ГБУЗ ЯО «КБ № 3», Ярославль, Россия. 

150000, Россия, г. Ярославль, ул. Революционная, д. 5.

150007, Россия, г. Ярославль, ул. Маяковского, д. 61.

Doctor of Sciences (Medicine), Professor, Head of the Department of Hospital Therapy of Yaroslavl State Medical University; therapist, chief researcher of Clinical Hospital No. 3, Yaroslavl, Russia. 

5, Revolutionary Str., Yaroslavl, Russia, 150000.

61, Mayakovskogo Str., Yaroslavl, Russia, 150007.

Noskov03@gmail.comhttps://orcid.org/0000-0002-2290-0013БалыковаЛ. А.BalykovaL. A.

доктор медицинских наук, профессор, член-корреспондент РАН, заведующий кафедрой педиатрии, директор Медицинского института ФГБОУ ВО «МГУ им. Н.П. Огарева». 

430005, Россия, г. Саранск, ул. Большевистская, д. 68

Doctor of Sciences (Medicine), Professor, Corresponding Member of the Russian Academy of Sciences, Head of the Department of Pediatrics, Director of National Research Ogarev Mordovia State University.

68, Bolshevistskaya Str., Saransk, Russia, 430005

 

larisabalykova@yandex.ruФедеральное государственное бюджетное образовательное учреждение дополнительного профессионального образования «Российская медицинская академия непрерывного профессионального образования» Министерства здравоохранения Российской ФедерацииРоссияRussian Medical Academy of Continuing Professional EducationRussian FederationОбщество с ограниченной ответственностью «Центр Фармацевтической Аналитики» (ООО «ЦФА»)РоссияLimited Liability Company “Center for Pharmaceutical Analytics”Russian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «МИРЭА – Российский технологический университет»РоссияMIREA – Russian Technological UniversityRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Московский государственный медико-стоматологический университет имени А.И. Евдокимова» Министерства здравоохранения Российской ФедерацииРоссияYevdokimov Moscow State Medical and Dental UniversityRussian FederationОбщество с ограниченной ответственностью «Практика здоровья»РоссияLimited Liability Company “Health Practice”Russian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Национальный исследовательский Мордовский государственный университет имени Н.П. Огарёва»РоссияNational Research Ogarev Mordovia State UniversityRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Тверской государственный медицинский университет Минздрава РоссииРоссияTver 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 автономное образовательное учреждение высшего образования «Первый Московский государственный медицинский университет имени И.М. Сеченова» Министерства здравоохранения Российской Федерации (Сеченовский Университет)РоссияSechenov First Moscow State Medical University (Sechenov 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 «Ярославский государственный медицинский университет» Министерства здравоохранения Российской Федерации. Государственное бюджетное учреждение здравоохранения Ярославской области «Клиническая больница № 3».РоссияYaroslavl State Medical University. Clinical Hospital No. 3.Russian Federation202309012024114324346Copyright © Аметов А.С., Шохин И.Е., Рогожина Е.А., Бодрова Т.Г., Невретдинова М.Е., Белый П.А., Заславская К.Я., Щербакова В.С., Куркин Д.В., Корянова К.Н., Мищенко Е.С., Кесова Э.Ю., Козлов Е.Д., Самошкина Е.С., Андреев Д.Н., Казаишвили Ю.Г., Носков С.М., Балыкова Л.А., 20242024Аметов А.С., Шохин И.Е., Рогожина Е.А., Бодрова Т.Г., Невретдинова М.Е., Белый П.А., Заславская К.Я., Щербакова В.С., Куркин Д.В., Корянова К.Н., Мищенко Е.С., Кесова Э.Ю., Козлов Е.Д., Самошкина Е.С., Андреев Д.Н., Казаишвили Ю.Г., Носков С.М., Балыкова Л.А.Ametov A.S., Shokhin I.E., Rogozhina E.A., Bodrova T.G., Nevretdinova M.E., Bely P.A., Zaslavskaya K.Y., Scherbakova V.S., Kurkin D.V., Koryanova K.N., Mishchenko E.S., Kesova E.Y., Kozlov E.D., Samoshkina E.S., Andreev D.N., Kazaishvili Y.G., Noskov S.M., Balykova L.A.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/1385

Семаглутид является представителем аналогов инкретинового гормона человеческого глюкагоноподобного пептида-1 (ГПП-1) и в настоящее время в России используется для лечения сахарного диабета 2 типа (СД 2; в монотерапии и в комбинированной терапии), в том числе у пациентов с ожирением и избыточной массой тела.

Цель

Цель. Провести сравнительную оценку физико-химических свойств, биологической активности, биоэквивалентности и безопасности, включая переносимость и иммуногенность, лекарственного препарата Квинсента® (семаглутид, 1,34 мг/мл, раствор для подкожного введения, ООО «Промомед», Россия) и препарата Оземпик® (семаглутид, 1,34 мг/мл, раствор для подкожного введения, Ново Нордиск А/С, Дания), при введении здоровым добровольцам.

Материалы и методы

Материалы и методы. Для оценки степени подобия исследуемого препарата Квинсента® (семаглутид, 1,34 мг/мл, раствор для подкожного введения, ООО «Промомед», Россия) с химически синтезированным активным веществом оригинальному (референтному) препарату Оземпик® (семаглутид, 1,34 мг/мл, раствор для подкожного введения, Ново Нордиск А/С, Дания) было проведено сравнительное изучение физико-химических свойств и биологической активности. Для оценки биоэквивалентности исследуемого и референтного препарата было проведено открытое рандомизированное параллельное сравнительное исследование с участием здоровых добровольцев (n=54), из них в популяцию для оценки биоэквивалентности вошли 54 участника. Добровольцы были рандомизированы в 2 группы в соотношении 1:1 и получали однократно подкожно утром натощак, либо исследуемый препарат (отечественный семаглутид в дозе 0,5 мг), либо референтный препарат (зарубежный семаглутид в дозе 0,5 мг). Концентрацию семаглутида определяли в образцах сыворотки крови с помощью предварительно валидированного метода иммуноферментного анализа (ИФА). Количественное определение антител к семаглутиду в сыворотке крови человека методом ИФА было проведено с помощью фотометра для микропланшетов с использованием готовых предварительно валидированных производителем наборов. Вывод о биоэквивалентности сравниваемых препаратов делали с использованием подхода, основанного на оценке 90% доверительных интервалов для отношений средних геометрических значений параметров Сmaх, AUC(0–t) семаглутида в исходных единицах измерения.

Результаты

Результаты. Результаты сравнительного анализа исследуемого и референтного препарата демонстрируют сопоставимость физико-химических свойств и биологической активности. Результаты клинического исследования продемонстрировали биоэквивалентность исследуемого препарата и препарата сравнения. Так, фармакокинетические параметры препаратов были сопоставимы между собой: величина Cmax для исследуемого препарата составила 42,088±8,827 нг/мл, для препарата сравнения Оземпик® данный показатель составил 42,2556±7,84. При этом период полувыведения для исследуемого препарата и препарата сравнения составил 168,39±39,47 и 157,99±28,57 ч, соответственно. Полученные 90%-ные доверительные интервалы для отношения значений Cmax и AUC0-t исследуемого препарата и референтного препарата составили 90,89–109,15 и 91,66–111,27%, соответственно. Переносимость препаратов у добровольцев была отмечена как хорошая. При проведении исследования не было зафиксировано нежелательных явлений. В течение всего исследования не было зарегистрировано ни одного серьёзного нежелательного явления. По результатам анализа иммуногенности у добровольцев не были выявлены антитела к семаглутиду российского производства в сыворотке крови, что свидетельствовало об отсутствии иммуногенности препарата.

Заключение

Заключение. В ходе проведенного исследования была подтверждена сопоставимость физико-химических свойств и биологической активности исследуемого российского препарата с химически синтезированным активным веществом Квинсента® препарату сравнения Оземпик®: диапазон активности исследуемых препаратов находился в пределах 80–120% по отношению к стандартному образцу семаглутида. Показана биоэквивалентность и сходный профиль безопасности, включая иммуногенность и переносимость российского препарата Квинсента® (семаглутид 1,34 мг/мл, ООО «Промомед», Россия) в сравнении с зарубежным препаратом Оземпик® (семаглутид 1,34 мг/мл, Ново Нордиск А/С, Дания).

Semaglutide is a representative of analogues of the incretin hormone human glucagon-like peptide-1 (GLP-1) and is currently used in Russia for the treatment of type 2 diabetes mellitus (T2DM; in monotherapy and in combination therapy), including patients with obesity and overweight.

The aim of the work was to conduct a comparative assessment of the physicochemical properties, a biological activity, bioequivalence and safety, including tolerability and immunogenicity, of the drug Quincent® (semaglutide, 1.34 mg/ml, a solution for a subcutaneous administration, Promomed Rus LLC, Russia) and the drug Ozempic® (semaglutide, 1.34 mg/ml, a solution for a subcutaneous administration, Novo Nordisk A/S, Denmark) when administered to healthy volunteers.

Materials and methods

Materials and methods. To assess the degree of similarity of the study drug Quincenta® (semaglutide, 1.34 mg/ml, a solution for a subcutaneous administration, Promomed Rus LLC, Russia) with a chemically synthesized active substance to the original (reference) drug Ozempic® (semaglutide, 1.34 mg/ml, a solution for a subcutaneous administration, Novo Nordisk A/S, Denmark), a comparative study of physicochemical properties and a biological activity was carried out. To assess the bioequivalence of the study drug and the reference drug, an open randomized parallel comparative study with the participation of healthy volunteers (n=54), 54 participants of which had been included in the population, was conducted. The volunteers were randomized into 2 groups in a 1:1 ratio, and received a single dose subcutaneously either of the study drug (domestic semaglutide at a dose of 0.5 mg) or the reference drug (foreign semaglutide at a dose of 0.5 mg). The mode of administration was in the morning on an empty stomach. A semaglutide concentration was determined in serum samples using a previously validated enzyme-linked immunosorbent assay (ELISA) method. A quantitative determination of antibodies to semaglutide in the human serum by ELISA was carried out with a microplate photometer using ready-made kits pre-validated by the manufacturer. The conclusion about the bioequivalence of the compared drugs was made using an approach based on the assessment of 90% confidence intervals for the ratios of the geometric mean values of the parameters Cmax, AUC(0–t) of semaglutide in the measurement original units.

Results

Results. The results of the comparative analysis of the study drug and the reference drug demonstrate the comparability of their physicochemical properties and biological activity. The results of the clinical study demonstrated the bioequivalence of the test drug and the reference drug. Thus, the pharmacokinetic parameters of the drugs were comparable to each other: the Cmax value for the study drug was 42.088±8.827 ng/ml, for the reference drug Ozempic® it was 42.2556±7.84. Herewith, the half-life for the study drug and the reference drug was 168.39±39.47 and 157.99±28.57 hours, respectively. The resulting 90% confidence intervals for the ratio of the Cmax and AUC0–t values of the study drug and the reference drug were 90.89–109.15 and 91.66–111.27%, respectively. The tolerability of the drugs in the volunteers was notified as good. No adverse events were recorded during the study. No serious adverse events were reported throughout the study. According to the results of the immunogenicity analysis, no antibodies to Russian-made semaglutide were detected in the blood serum of the volunteers, which indicated the lack of Results. The results of a comparative analysis of the study drug and the reference drug demonstrate the comparability of physicochemical properties and biological activity. The results of the clinical study demonstrated the bioequivalence of the study drug and the reference drug. Thus, the pharmacokinetic parameters of the drugs were comparable to each other: the Cmax value for the study drug was 42.088±8.827 ng/ml, for the reference drug Ozempic® this figure was 42.2556±7.84. At the same time, the half-life for the study drug and the reference drug was 168.39±39.47 and 157.99±28.57 hours, respectively. The resulting 90% confidence intervals for the ratio of the Cmax and AUC0–t values of the study drug and the reference drug were 90.89–109.15 and 91.66–111.27%, respectively. Tolerability of the drugs in volunteers was noted as good. No adverse events were recorded during the study. No serious adverse events were reported throughout the study. According to the results of the immunogenicity analysis, no antibodies to Russian-made semaglutide were detected in the blood serum of the volunteers, which indicated the lack of the drug immunogenicity.

Conclusion

Conclusion. In the course of the study, the comparability of the physicochemical properties and biological activity of the studied Russian drug with the chemically synthesized active substance Quincenta® to the reference drug Ozempic® was confirmed: the activity range of the studied drugs was within 80–120% in relation to the standard sample of semaglutide. The bioequivalence and a similar safety profile, including the immunogenicity and tolerability of the Russian drug Quincenta® (semaglutide 1.34 mg/ml, Promomed Rus LLC, Russia) were shown in comparison with the foreign drug Ozempic® (semaglutide 1.34 mg/ml, Novo Nordisk A/C, Denmark).

глюкагоноподобный пептид-1ГПП-1биоэквивалентностьфармакокинетикасемаглутидсахарный диабет 2-го типафизико-химические свойствапрофиль безопасностибиологическая активностьglucagon-like peptide-1GLP-1bioequivalencepharmacokineticssemaglutidetype 2 diabetes mellitusphysicochemical propertiessafety profilebiological activityКлиническое исследование проводилось при поддержке компании ООО «Промомед Рус». Спонсор не оказывал влияние на выбор материала для публикации, анализ и интерпретацию данных.The clinical study was conducted with the support of Promomed RUS LLC. The sponsor had no influence on the selection of material for publication, analysis or interpretation of data.ReferencesGarber A.J., Handelsman Y., Grunberger G., Einhorn D., Abrahamson M.J., Barzilay J.I., Blonde L., Bush M.A., DeFronzo R.A., Garber J.R., Garvey W.T., Hirsch I.B., Jellinger P.S., McGill J.B., Mechanick J.I., Perreault L., Rosenblit P.D., Samson S., Umpierrez G.E. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm – 2020 EXECUTIVE SUMMARY // Endocr Pract. – 2020. – Vol. 26, No. 1. – P. 107–139. DOI: 10.4158/CS-2019-0472Garber AJ, Handelsman Y, Grunberger G, Einhorn D, Abrahamson MJ, Barzilay JI, Blonde L, Bush MA, DeFronzo RA, Garber JR, Garvey WT, Hirsch IB, Jellinger PS, McGill JB, Mechanick JI, Perreault L, Rosenblit PD, Samson S, Umpierrez GE. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm – 2020 EXECUTIVE SUMMARY. Endocr Pract. 2020;26(1):107–39. DOI: 10.4158/CS-2019-0472Алгоритмы специализированной медицинской помощи больным сахарным диабетом / Под редакцией И.И. Дедова, М.В. Шестаковой, А.Ю. Майорова. 11-й выпуск // Сахарный диабет. – 2023. – Т. 26, № 2S. – С. 1–231. DOI: 10.14341/DM13042Algorithms for specialized medical care for patients with diabetes mellitus. Dedova II, Shestakova MV, Mayorova AYu, editors. 11th issue. Diabetes mellitus. 2023;26(2S):1–231. DOI: 10.14341/DM13042Bancks M.P., Ning H., Allen N.B., Bertoni A.G., Carnethon M.R., Correa A., Echouffo-Tcheugui J.B., Lange L.A., Lloyd-Jones D.M., Wilkins J.T. Long-term absolute risk for cardiovascular disease stratified by fasting glucose level // Diabetes Care. – 2019. – Vol. 42, No. 3. – P. 457–465. DOI: 10.2337/dc18-1773Bancks MP, Ning H, Allen NB, Bertoni AG, Carnethon MR, Correa A, Echouffo-Tcheugui JB, Lange LA, Lloyd-Jones DM, Wilkins JT. Long-term absolute risk for cardiovascular disease stratified by fasting glucose level. Diabetes Care. 2019;42(3):457–65. DOI: 10.2337/dc18-1773Emerging Risk Factors Collaboration; Sarwar N., Gao P., Seshasai S.R., Gobin R., Kaptoge S., Di Angelantonio E., Ingelsson E., Lawlor D.A., Selvin E., Stampfer M., Stehouwer C.D., Lewington S., Pennells L., Thompson A., Sattar N., White I.R., Ray K.K., Danesh J. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies // Lancet. – 2010. – Vol. 375, No. 9733. – P. 2215–2222. DOI: 10.1016/S0140-6736(10)60484-9. Erratum in: Lancet. – 2010. – Vol. 376, No. 9745. – P. 958.Emerging Risk Factors Collaboration; Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, Ingelsson E, Lawlor DA, Selvin E, Stampfer M, Stehouwer CD, Lewington S, Pennells L, Thompson A, Sattar N, White IR, Ray KK, Danesh J. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010;375(9733):2215–22. DOI: 10.1016/S0140-6736(10)60484-9. Erratum in: Lancet. 2010;376(9745):958.Gaede P., Lund-Andersen H., Parving H.H., Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes // N Engl J Med. – 2008. – Vol. 358, No. 6. – P. 580–91. DOI: 10.1056/NEJMoa0706245Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med. 2008 Feb 7;358(6):580–91. DOI: 10.1056/NEJMoa0706245Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group // Lancet. 1998. – Vol. 352, No. 9131. – P. 837–853. Erratum in: Lancet. – 1999. – Vol. 354, No. 9178. – P. 602.Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352(9131):837–53. Erratum in: Lancet 1999;354(9178):602.Raghavan S., Vassy J.L., Ho Y.L., Song R.J., Gagnon D.R., Cho K., Wilson P.W.F., Phillips L.S. Diabetes mellitus-related all-cause and cardiovascular mortality in a national cohort of adults // J Am Heart Assoc. – 2019. – Vol. 8, No. 4. – P. e011295. DOI: 10.1161/JAHA.118.011295Raghavan S, Vassy JL, Ho YL, Song RJ, Gagnon DR, Cho K, Wilson PWF, Phillips LS. Diabetes mellitus-related all-cause and cardiovascular mortality in a national cohort of adults. J Am Heart Assoc. 2019;8(4):e011295. DOI: 10.1161/JAHA.118.011295Svensson E., Baggesen L.M., Johnsen S.P., Pedersen L., Nørrelund H., Buhl E.S., Haase C.L., Thomsen R.W. Early glycemic control and magnitude of hba1c reduction predict cardiovascular events and mortality: population-based cohort study of 24,752 metformin initiators // Diabetes Care. – 2017. – Vol. 40, No. 6. – P. 800–807. DOI: 10.2337/dc16-2271Svensson E, Baggesen LM, Johnsen SP, Pedersen L, Nørrelund H, Buhl ES, Haase CL, Thomsen RW. Early glycemic control and magnitude of hba1c reduction predict cardiovascular events and mortality: population-based cohort study of 24,752 metformin initiators. Diabetes Care. 2017;40(6):800–7. DOI: 10.2337/dc16-2271Mannucci E., Dicembrini I., Lauria A., Pozzilli P. Is glucose control important for prevention of cardiovascular disease in diabetes? // Diabetes Care. – 2013. – Vol. 36, Suppl 2. – P. S259–S263. DOI: 10.2337/dcS13-2018Mannucci E, Dicembrini I, Lauria A, Pozzilli P. Is glucose control important for prevention of cardiovascular disease in diabetes? Diabetes Care. 2013;36(Suppl 2):S259–S63. DOI: 10.2337/dcS13-2018ElSayed N.A., Aleppo G., Aroda V.R., Bannuru R.R., Brown F.M., Bruemmer D., Collins B.S., Hilliard M.E., Isaacs D., Johnson E.L., Kahan S., Khunti K., Leon J., Lyons S.K., Perry M.L., Prahalad P., Pratley R.E., Seley J.J., Stanton R.C., Gabbay R.A., on behalf of the American Diabetes Association. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2023 // Diabetes Care. – 2023. – Vol. 46, Suppl 1. – P. S140–S157. DOI: 10.2337/dc23-S009ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, Collins BS, Hilliard ME, Isaacs D, Johnson EL, Kahan S, Khunti K, Leon J, Lyons SK, Perry ML, Prahalad P, Pratley RE, Seley JJ, Stanton RC, Gabbay RA, on behalf of the American Diabetes Association. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2023. Diabetes Care. 2023;46(Suppl 1):S140–57. DOI: 10.2337/dc23-S009Knudsen L.B., Lau J. The discovery and development of liraglutide and semaglutide // Front Endocrinol (Lausanne). – 2019. – Vol. 10. – Art. ID: 155. DOI: 10.3389/fendo.2019.00155Knudsen LB, Lau J. The discovery and development of liraglutide and semaglutide. Front Endocrinol (Lausanne). 2019;10:155. DOI: 10.3389/fendo.2019.00155Kristensen S.L., Rørth R., Jhund P.S., Docherty K.F., Sattar N., Preiss D., Køber L., Petrie M.C., McMurray J.J.V. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials // Lancet Diabetes Endocrinol. – 2019. – Vol. 7, No. 10. – P. 776–785. DOI: 10.1016/S2213-8587(19)30249-9. Erratum in: Lancet Diabetes Endocrinol. – 2020. – Vol. 8, No. 3. – P. e2.Kristensen SL, Rørth R, Jhund PS, Docherty KF, Sattar N, Preiss D, Køber L, Petrie MC, McMurray JJV. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019;7(10):776–85. DOI: 10.1016/S2213-8587(19)30249-9. Erratum in: Lancet Diabetes Endocrinol. 2020;8(3):e2.Yu M., Benjamin M.M., Srinivasan S., Morin E.E., Shishatskaya E.I., Schwendeman S.P., Schwendeman A. Battle of GLP-1 delivery technologies // Adv Drug Deliv Rev. – 2018. – Vol. 130. – P. 113–130. DOI: 10.1016/j.addr.2018.07.009Yu M, Benjamin MM, Srinivasan S, Morin EE, Shishatskaya EI, Schwendeman SP, Schwendeman A. Battle of GLP-1 delivery technologies. Adv Drug Deliv Rev. 2018;130:113–30. DOI: 10.1016/j.addr.2018.07.009Hussein H., Zaccardi F., Khunti K., Davies M.J., Patsko E., Dhalwani N.N., Kloecker D.E., Ioannidou E., Gray L.J. Efficacy and tolerability of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists: A systematic review and network meta-analysis // Diabetes Obes Metab. – 2020. – Vol. 22, No. 7. – P. 1035–1046. DOI: 10.1111/dom.14008Hussein H, Zaccardi F, Khunti K, Davies MJ, Patsko E, Dhalwani NN, Kloecker DE, Ioannidou E, Gray LJ. Efficacy and tolerability of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists: A systematic review and network meta-analysis. Diabetes Obes Metab. 2020;22(7):1035–46. DOI: 10.1111/dom.14008Lyseng-Williamson K.A. Glucagon-like peptide-1 receptor analogues in type 2 diabetes: their use and differential features // Clin Drug Investig. – 2019. – Vol. 39, No. 8. – P. 805–819. DOI: 10.1007/s40261-019-00826-0. Erratum in: Clin Drug Investig. – 2019. Erratum in: Clin Drug Investig. – 2019. Erratum in: Clin Drug Investig. – 2020. – Vol. 40, No. 3. – P. 291.Lyseng-Williamson KA. Glucagon-like peptide-1 receptor analogues in type 2 diabetes: their use and differential features. clin drug investig. 2019;39(8):805–19. DOI: 10.1007/s40261-019-00826-0. Erratum in: Clin Drug Investig. 2019. Erratum in: Clin Drug Investig. 2019. Erratum in: Clin Drug Investig. 2020;40(3):291.Карпов Ю.А., Старостина Е.Г. Семаглутид (Оземпик) с точки зрения эндокринолога и кардиолога: возможности аналогов глюкагоноподобного пептида-1 далеко не исчерпаны // Атмосфера. Новости кардиологии. – 2019. – № 4. – С. 3–17. DOI: 10.24411/2076-4189-2019-12170Karpov YuA, Starostina E.G. Semaglutide (Ozempic) from the point of view of endocrinologist and cardiologist: the possibilities of glucagon-like peptide-1 analogues are far from exhausted. Atmosphere. Cardiology News. 2019;(4):3–17. DOI: 10.24411/2076-4189-2019-12170Kapitza C., Nosek L., Jensen L., Hartvig H., Jensen C.B., Flint A. Semaglutide, a once-weekly human GLP-1 analog, does not reduce the bioavailability of the combined oral contraceptive, ethinylestradiol/levonorgestrel // J Clin Pharmacol. – 2015. – Vol. 55, No. 5. – P. 497–504. DOI: 10.1002/jcph.443Kapitza C, Nosek L, Jensen L, Hartvig H, Jensen CB, Flint A. Semaglutide, a once-weekly human GLP-1 analog, does not reduce the bioavailability of the combined oral contraceptive, ethinylestradiol/levonorgestrel. J Clin Pharmacol. 2015;55(5):497–504. DOI: 10.1002/jcph.443Kapitza C., Dahl K., Jacobsen J.B., Axelsen M.B., Flint A. Effects of semaglutide on beta cell function and glycaemic control in participants with type 2 diabetes: a randomised, double-blind, placebo-controlled trial // Diabetologia. – 2017. – Vol. 60, No. 8. – P. 1390–1399. DOI: 10.1007/s00125-017-4289-0Kapitza C, Dahl K, Jacobsen JB, Axelsen MB, Flint A. Effects of semaglutide on beta cell function and glycaemic control in participants with type 2 diabetes: a randomised, double-blind, placebo-controlled trial. Diabetologia. 2017;60(8):1390–9. DOI: 10.1007/s00125-017-4289-0Nauck M.A., Petrie J.R., Sesti G., Mannucci E., Courrèges J.P., Lindegaard M.L., Jensen C.B., Atkin S.L.; Study 1821 Investigators. A phase 2, randomized, dose-finding study of the novel once-weekly human GLP-1 analog, semaglutide, compared with placebo and open-label liraglutide in patients with type 2 diabetes // Diabetes Care. – 2016. – Vol. 39, No. 2. – P. 231–241. DOI: 10.2337/dc15-0165Nauck MA, Petrie JR, Sesti G, Mannucci E, Courrèges JP, Lindegaard ML, Jensen CB, Atkin SL; Study 1821 Investigators. A phase 2, randomized, dose-finding study of the novel once-weekly human GLP-1 analog, semaglutide, compared with placebo and open-label liraglutide in patients with type 2 diabetes. Diabetes Care. 2016;39(2):231–41. DOI: 10.2337/dc15-0165Marbury T.C., Flint A., Jacobsen J.B., Derving Karsbøl J., Lasseter K. Pharmacokinetics and tolerability of a single dose of semaglutide, a human glucagon-like peptide-1 analog, in subjects with and without renal impairment // Clin Pharmacokinet. – 2017. – Vol. 56, No. 11. – P. 1381–1390. DOI: 10.1007/s40262-017-0528-2Marbury TC, Flint A, Jacobsen JB, Derving Karsbøl J, Lasseter K. Pharmacokinetics and tolerability of a single dose of semaglutide, a human glucagon-like peptide-1 analog, in subjects with and without renal impairment. Clin Pharmacokinet. 2017;56(11):1381–90. DOI: 10.1007/s40262-017-0528-2Jensen L., Kupcova V., Arold G., Pettersson J., Hjerpsted J.B. Pharmacokinetics and tolerability of semaglutide in people with hepatic impairment // Diabetes Obes Metab. – 2018. – Vol. 20, No. 4. – P. 998–1005. DOI: 10.1111/dom.13186Jensen L, Kupcova V, Arold G, Pettersson J, Hjerpsted JB. Pharmacokinetics and tolerability of semaglutide in people with hepatic impairment. Diabetes Obes Metab. 2018;20(4):998–1005. DOI: 10.1111/dom.13186Jensen L., Helleberg H., Roffel A., van Lier J.J., Bjørnsdottir I., Pedersen P.J., Rowe E., Derving Karsbøl J., Pedersen M.L. Absorption, metabolism and excretion of the GLP-1 analogue semaglutide in humans and nonclinical species // Eur J Pharm Sci. – 2017. – Vol. 104. – P. 31–41. DOI: 10.1016/j.ejps.2017.03.020Jensen L, Helleberg H, Roffel A, van Lier JJ, Bjørnsdottir I, Pedersen PJ, Rowe E, Derving Karsbøl J, Pedersen ML. Absorption, metabolism and excretion of the GLP-1 analogue semaglutide in humans and nonclinical species. Eur J Pharm Sci. 2017;104:31–41. DOI: 10.1016/j.ejps.2017.03.020Baekdal T.A., Thomsen M., Kupčová V., Hansen C.W., Anderson T.W. Pharmacokinetics, Safety, and tolerability of oral semaglutide in subjects with hepatic impairment // J Clin Pharmacol. – 2018. – Vol. 58, No. 10. – P. 1314–1323. DOI: 10.1002/jcph.1131Baekdal TA, Thomsen M, Kupčová V, Hansen CW, Anderson TW. Pharmacokinetics, Safety, and Tolerability of Oral Semaglutide in Subjects With Hepatic Impairment. J Clin Pharmacol. 2018;58(10):1314–23. DOI: 10.1002/jcph.1131Blundell J., Finlayson G., Axelsen M., Flint A., Gibbons C., Kvist T., Hjerpsted J.B. Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity // Diabetes Obes Metab. – 2017. – Vol. 19, No. 9. – P. 1242–1251. DOI: 10.1111/dom.12932Blundell J, Finlayson G, Axelsen M, Flint A, Gibbons C, Kvist T, Hjerpsted JB. Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity. Diabetes Obes Metab. 2017;19(9):1242–51. DOI: 10.1111/dom.12932Johnson-Agbakwu C., Brown L., Yuan J., Kissling R., Greenblatt D.J. Effects of flibanserin on the pharmacokinetics of a combined ethinylestradiol/levonorgestrel oral contraceptive in healthy premenopausal women: a randomized crossover study // Clin Ther. – 2018. – Vol. 40, No. 1. – P. 64–73. DOI: 10.1016/j.clinthera.2017.08.021Johnson-Agbakwu C, Brown L, Yuan J, Kissling R, Greenblatt DJ. Effects of Flibanserin on the Pharmacokinetics of a Combined Ethinylestradiol/Levonorgestrel Oral Contraceptive in Healthy Premenopausal Women: A Randomized Crossover Study. Clin Ther. 2018;40(1):64–73. DOI: 10.1016/j.clinthera.2017.08.021Granhall C., Søndergaard F.L., Thomsen M., Anderson T.W. Pharmacokinetics, Safety and Tolerability of Oral Semaglutide in Subjects with Renal Impairment // Clin Pharmacokinet. – 2018. – Vol. 57, No. 12. – P. 1571–1580. DOI: 10.1007/s40262-018-0649-2Granhall C, Søndergaard FL, Thomsen M, Anderson TW. Pharmacokinetics, Safety and Tolerability of Oral Semaglutide in Subjects with Renal Impairment. Clin Pharmacokinet. 2018;57(12):1571–80. DOI: 10.1007/s40262-018-0649-2Sorli C., Harashima S.I., Tsoukas G.M., Unger J., Karsbøl J.D., Hansen T., Bain S.C. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial // Lancet Diabetes Endocrinol. – 2017. – Vol. 5, No. 4. – P. 251–260. DOI: 10.1016/S2213-8587(17)30013-XSorli C, Harashima SI, Tsoukas GM, Unger J, Karsbøl JD, Hansen T, Bain SC. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. Lancet Diabetes Endocrinol. 2017;5(4):251–60. DOI: 10.1016/S2213-8587(17)30013-XAhrén B., Masmiquel L., Kumar H., Sargin M., Karsbøl J.D., Jacobsen S.H., Chow F. Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial // Lancet Diabetes Endocrinol. – 2017. – Vol. 5, No. 5. – P. 341–354. DOI: 10.1016/S2213-8587(17)30092-XAhrén B, Masmiquel L, Kumar H, Sargin M, Karsbøl JD, Jacobsen SH, Chow F. Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial. Lancet Diabetes Endocrinol. 2017;5(5):341–54. DOI: 10.1016/S2213-8587(17)30092-XAhmann A.J., Capehorn M., Charpentier G., Dotta F., Henkel E., Lingvay I., Holst A.G., Annett M.P., Aroda V.R. Efficacy and safety of once-weekly semaglutide versus exenatide ER in subjects with type 2 diabetes (SUSTAIN 3): a 56-week, open-label, randomized clinical trial // Diabetes Care. – 2018. – Vol. 41, No. 2. – P. 258–266. DOI: 10.2337/dc17-0417Ahmann AJ, Capehorn M, Charpentier G, Dotta F, Henkel E, Lingvay I, Holst AG, Annett MP, Aroda VR. Efficacy and safety of once-weekly semaglutide versus exenatide ER in subjects with type 2 diabetes (SUSTAIN 3): a 56-week, open-label, randomized clinical trial. Diabetes Care. 2018;41(2):258–66. DOI: 10.2337/dc17-0417Aroda V.R., Bain S.C., Cariou B., Piletič M., Rose L., Axelsen M., Rowe E., DeVries J.H. Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial // Lancet Diabetes Endocrinol. – 2017. – Vol. 5, No. 5. – P. 355–366. DOI: 10.1016/S2213-8587(17)30085-2Aroda VR, Bain SC, Cariou B, Piletič M, Rose L, Axelsen M, Rowe E, DeVries JH. Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial. Lancet Diabetes Endocrinol. 2017;5(5):355–66. DOI: 10.1016/S2213-8587(17)30085-2Rodbard H.W., Lingvay I., Reed J., de la Rosa R., Rose L., Sugimoto D., Araki E., Chu P.L., Wijayasinghe N., Norwood P. Semaglutide added to basal insulin in type 2 diabetes (SUSTAIN 5): a randomized, controlled trial // J Clin Endocrinol Metab. – 2018. – Vol. 103, No. 6. – P. 2291–2301. DOI: 10.1210/jc.2018-00070Rodbard HW, Lingvay I, Reed J, de la Rosa R, Rose L, Sugimoto D, Araki E, Chu PL, Wijayasinghe N, Norwood P. Semaglutide added to basal insulin in type 2 diabetes (SUSTAIN 5): a randomized, controlled trial. J Clin Endocrinol Metab. 2018;103(6):2291–301. DOI: 10.1210/jc.2018-00070Pratley R.E., Aroda V.R., Lingvay I., Lüdemann J., Andreassen C., Navarria A., Viljoen A.; SUSTAIN 7 investigators. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial // Lancet Diabetes Endocrinol. – 2018. – Vol. 6, No. 4. – P. 275–286. DOI: 10.1016/S2213-8587(18)30024-XPratley RE, Aroda VR, Lingvay I, Lüdemann J, Andreassen C, Navarria A, Viljoen A; SUSTAIN 7 investigators. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. Lancet Diabetes Endocrinol. 2018;6(4):275–86. DOI: 10.1016/S2213-8587(18)30024-XNapoli R., Berra C., Catarig A.M., Di Loreto C., Donatiello E., Berentzen T.L., Pitocco D., Giorgino F. Once-weekly semaglutide use in patients with type 2 diabetes: Real-world data from the SURE Italy observational study // Diabetes Obes Metab. – 2023. – Vol. 25, No. 6. – P. 1658–1667. DOI: 10.1111/dom.15020Napoli R, Berra C, Catarig AM, Di Loreto C, Donatiello E, Berentzen TL, Pitocco D, Giorgino F. Once-weekly semaglutide use in patients with type 2 diabetes: Real-world data from the SURE Italy observational study. Diabetes Obes Metab. 2023;25(6):1658–67. DOI: 10.1111/dom.15020Wolffenbuttel B.H.R., Brugts M.P., Catarig A.M., Clark A., Kok M., Lieverse A.G., van Soest J. Once-weekly semaglutide use in type 2 diabetes: real-world data from the SURE Netherlands observational study // Adv Ther. – 2023. – Vol. 40, No. 3. – P. 920–933. DOI: 10.1007/s12325-022-02385-xWolffenbuttel BHR, Brugts MP, Catarig AM, Clark A, Kok M, Lieverse AG, van Soest J. Once-Weekly Semaglutide Use in Type 2 Diabetes: Real-World Data from the SURE Netherlands Observational Study. Adv Ther. 2023;40(3):920–33. DOI: 10.1007/s12325-022-02385-xDi Folco U., Vallecorsa N., Nardone M.R., Pantano A.L., Tubili C. Effects of semaglutide on cardiovascular risk factors and eating behaviors in type 2 diabetes // Acta Diabetol. – 2022. – Vol. 59, No. 10. – P. 1287–1294. DOI: 10.1007/s00592-022-01936-6Di Folco U, Vallecorsa N, Nardone MR, Pantano AL, Tubili C. Effects of semaglutide on cardiovascular risk factors and eating behaviors in type 2 diabetes. Acta Diabetol. 2022;59(10):1287–94. DOI: 10.1007/s00592-022-01936-6Witkowski M., Wilkinson L., Webb N., Weids A., Glah D., Vrazic H. A Systematic literature review and network meta-analysis comparing once-weekly semaglutide with other glp-1 receptor agonists in patients with type 2 diabetes previously receiving 1-2 oral anti-diabetic drugs // Diabetes Ther. – 2018. – Vol. 9, No. 3. – P. 1149–1167. DOI: 10.1007/s13300-018-0424-2Witkowski M, Wilkinson L, Webb N, Weids A, Glah D, Vrazic H. A Systematic Literature Review and Network Meta-Analysis Comparing Once-Weekly Semaglutide with Other GLP-1 Receptor Agonists in Patients with Type 2 Diabetes Previously Receiving 1-2 Oral Anti-Diabetic Drugs. Diabetes Ther. 2018;9(3):1149–67. DOI: 10.1007/s13300-018-0424-2Kanters S., Wilkinson L., Vrazic H., Sharma R., Lopes S., Popoff E., Druyts E. Comparative efficacy of once-weekly semaglutide versus SGLT-2 inhibitors in patients inadequately controlled with one to two oral antidiabetic drugs: a systematic literature review and network meta-analysis // BMJ Open. – 2019. – Vol. 9, No. 7. – P. e023458. DOI: 10.1136/bmjopen-2018-023458.Kanters S, Wilkinson L, Vrazic H, Sharma R, Lopes S, Popoff E, Druyts E. Comparative efficacy of once-weekly semaglutide versus SGLT-2 inhibitors in patients inadequately controlled with one to two oral antidiabetic drugs: a systematic literature review and network meta-analysis. BMJ Open. 2019;9(7):e023458. DOI: 10.1136/bmjopen-2018-023458.Hu S., Su X., Fan G. Efficacy and tolerability of the Subcutaneous Semaglutide for type 2 Diabetes patients: an updated systematic review and meta-analysis // Diabetol Metab Syndr. – 2023. – Vol. 15. – P. 218. DOI: 10.1186/s13098-023-01195-7Hu S, Su X, Fan G. Efficacy and tolerability of the Subcutaneous Semaglutide for type 2 Diabetes patients: an updated systematic review and meta-analysis. Diabetol Metab Syndr. 2023;15:218. DOI: 10.1186/s13098-023-01195-7Romera I., Cebrián-Cuenca A., Álvarez-Guisasola F., Gomez-Peralta F., Reviriego J. A review of practical issues on the use of glucagon-like peptide-1 receptor agonists for the management of type 2 diabetes // Diabetes Ther. – 2019. – Vol. 10, No. 1. – P. 5–19. DOI: 10.1007/s13300-018-0535-9Romera I, Cebrián-Cuenca A, Álvarez-Guisasola F, Gomez-Peralta F, Reviriego J. A Review of Practical Issues on the Use of Glucagon-Like Peptide-1 Receptor Agonists for the Management of Type 2 Diabetes. Diabetes Ther. 2019;10(1):5–19. DOI: 10.1007/s13300-018-0535-9Leiter L.A., Bain S.C., Bhatt D.L., Buse J.B., Mazer C.D., Pratley R.E., Rasmussen S., Ripa M.S., Vrazic H., Verma S. The effect of glucagon-like peptide-1 receptor agonists liraglutide and semaglutide on cardiovascular and renal outcomes across baseline blood pressure categories: Analysis of the LEADER and SUSTAIN 6 trials // Diabetes Obes Metab. – 2020. – Vol. 22, No. 9. – P. 1690–1695. DOI: 10.1111/dom.14079Leiter LA, Bain SC, Bhatt DL, Buse JB, Mazer CD, Pratley RE, Rasmussen S, Ripa MS, Vrazic H, Verma S. The effect of glucagon-like peptide-1 receptor agonists liraglutide and semaglutide on cardiovascular and renal outcomes across baseline blood pressure categories: Analysis of the LEADER and SUSTAIN 6 trials. Diabetes Obes Metab. 2020;22(9):1690–5. DOI: 10.1111/dom.14079Husain M., Bain S.C., Holst A.G., Mark T., Rasmussen S., Lingvay I. Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials // Cardiovasc Diabetol. – 2020. – Vol. 19, No. 1. – P. 156. DOI: 10.1186/s12933-020-01106-4Husain M, Bain SC, Holst AG, Mark T, Rasmussen S, Lingvay I. Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials. Cardiovasc Diabetol. 2020;19(1):156. DOI: 10.1186/s12933-020-01106-4Wilding J.P.H., Batterham R.L., Calanna S., Davies M., Van Gaal L.F., Lingvay I., McGowan B.M., Rosenstock J., Tran M.T.D., Wadden T.A., Wharton S., Yokote K., Zeuthen N., Kushner R.F.; STEP 1 Study Group. once-weekly semaglutide in adults with overweight or obesity // N Engl J Med. – 2021. – Vol. 384, No. 11. – P. 989–1002. DOI: 10.1056/NEJMoa2032183Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989–1002. DOI: 10.1056/NEJMoa2032183Wadden T.A., Bailey T.S., Billings L.K., Davies M., Frias J.P., Koroleva A., Lingvay I., O’Neil P.M., Rubino D.M., Skovgaard D., Wallenstein S.O.R., Garvey W.T.; STEP 3 Investigators. Effect of subcutaneous semaglutide vs placebo as an adjunct to intensive behavioral therapy on body weight in adults with overweight or obesity: The STEP 3 Randomized Clinical Trial // JAMA. – 2021. – Vol. 325, No. 14. – P. 1403–1413. DOI: 10.1001/jama.2021.1831Wadden TA, Bailey TS, Billings LK, Davies M, Frias JP, Koroleva A, Lingvay I, O’Neil PM, Rubino DM, Skovgaard D, Wallenstein SOR, Garvey WT; STEP 3 Investigators. Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial. JAMA. 2021;325(14):1403–13. DOI: 10.1001/jama.2021.1831Rubino D., Abrahamsson N., Davies M., Hesse D., Greenway FL., Jensen C., Lingvay I., Mosenzon O., Rosenstock J., Rubio M.A., Rudofsky G., Tadayon S., Wadden T.A., Dicker D.; STEP 4 Investigators. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: The STEP 4 Randomized Clinical Trial // JAMA. – 2021. – Vol. 325, No. 14. – P. 1414–1425. DOI: 10.1001/jama.2021.3224Rubino D, Abrahamsson N, Davies M, Hesse D, Greenway FL, Jensen C, Lingvay I, Mosenzon O, Rosenstock J, Rubio MA, Rudofsky G, Tadayon S, Wadden TA, Dicker D; STEP 4 Investigators. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: The STEP 4 Randomized Clinical Trial. JAMA. 2021;325(14):1414–25. DOI: 10.1001/jama.2021.3224Rubino D.M., Greenway F.L., Khalid U., O’Neil P.M., Rosenstock J., Sørrig R., Wadden T.A., Wizert A., Garvey W.T.; STEP 8 Investigators. Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: The STEP 8 Randomized Clinical Trial // JAMA. – 2022. – Vol. 327, No. 2. – P. 138–150. DOI: 10.1001/jama.2021.23619Rubino DM, Greenway FL, Khalid U, O’Neil PM, Rosenstock J, Sørrig R, Wadden TA, Wizert A, Garvey WT; STEP 8 Investigators. Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: the step 8 randomized clinical trial. JAMA. 2022;327(2):138–50. DOI: 10.1001/jama.2021.23619Garvey W.T., Batterham R.L., Bhatta M., Buscemi S., Christensen L.N., Frias J.P., Jódar E., Kandler K., Rigas G., Wadden T.A., Wharton S.; STEP 5 Study Group. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial // Nat Med. – 2022. – Vol. 28, No. 10. – P. 2083–2091. DOI: 10.1038/s41591-022-02026-4Garvey WT, Batterham RL, Bhatta M, Buscemi S, Christensen LN, Frias JP, Jódar E, Kandler K, Rigas G, Wadden TA, Wharton S; STEP 5 Study Group. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nat Med. 2022;28(10):2083–91. DOI: 10.1038/s41591-022-02026-4Davies M., Færch L., Jeppesen O.K., Pakseresht A., Pedersen S.D., Perreault L., Rosenstock J., Shimomura I., Viljoen A., Wadden T.A., Lingvay I.; STEP 2 Study Group. Semaglutide 2•4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial // Lancet. – 2021. – Vol. 397, No. 10278. – P. 971–984. DOI: 10.1016/S0140-6736(21)00213-0Davies M, Færch L, Jeppesen OK, Pakseresht A, Pedersen SD, Perreault L, Rosenstock J, Shimomura I, Viljoen A, Wadden TA, Lingvay I; STEP 2 Study Group. Semaglutide 2•4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet. 2021; 397(10278):971–84. DOI: 10.1016/S0140-6736(21)00213-0Bandyopadhyay S., Das S., Samajdar S.S., Joshi S.R. Role of semaglutide in the treatment of nonalcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis // Diabetes Metab Syndr. – 2023. – Vol. 17, No. 10. – P. 102849. DOI: 10.1016/j.dsx.2023.102849Bandyopadhyay S, Das S, Samajdar SS, Joshi SR. Role of semaglutide in the treatment of nonalcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis. Diabetes Metab Syndr. 2023;17(10):102849. DOI: 10.1016/j.dsx.2023.102849Gumieniczek A., Berecka-Rycerz A. Metabolism and chemical degradation of new antidiabetic drugs: a review of analytical approaches for analysis of glutides and gliflozins // Biomedicines. – 2023. – Vol. 11, No. 8. – P. 2127. DOI: 10.3390/biomedicines11082127Gumieniczek A, Berecka-Rycerz A. Metabolism and Chemical Degradation of New Antidiabetic Drugs: A Review of Analytical Approaches for Analysis of Glutides and Gliflozins. Biomedicines. 2023;11(8):2127. DOI: 10.3390/biomedicines11082127D’Hondt M., Bracke N., Taevernier L., Gevaert B., Verbeke F., Wynendaele E., De Spiegeleer B. Related impurities in peptide medicines // J Pharm Biomed Anal. – 2014. – Vol. 101. – P. 2–30. DOI: 10.1016/j.jpba.2014.06.012D’Hondt M, Bracke N, Taevernier L, Gevaert B, Verbeke F, Wynendaele E, De Spiegeleer B. Related impurities in peptide medicines. J Pharm Biomed Anal. 2014;101:2–30. DOI: 10.1016/j.jpba.2014.06.012Li X., Fu Y., Zhang L., Yao L., Li W. Preparation method for semaglutide. WO2021143073A1, 2021.Li X, Fu Y, Zhang L, Yao L, Li W, inventors. Preparation method for semaglutide. WO2021143073A1. 2021.Lester J., Lobo M., Chandrakesan C., Doshi S., Lalchand C., Nandlal GY., Nikhil UM., Kodandaraman V. An improved process for fmoc synthesis of semaglutide. WO2023012709A1, 2023.Lester J, Lobo M, Chandrakesan C, Doshi S, Lalchand C, Nandlal GY, Nikhil UM, Kodandaraman V, inventors. An improved process for fmoc synthesis of semaglutide. WO2023012709A1. 2023.Zhang B., Xu W., Yin C., Tang Y. Characterization of low-level D-amino acid isomeric impurities of Semaglutide using liquid chromatography-high resolution tandem mass spectrometry // J Pharm Biomed Anal. – 2023. – Vol. 224. – Art. ID: 115164. DOI: 10.1016/j.jpba.2022.115164Zhang B, Xu W, Yin C, Tang Y. Characterization of low-level D-amino acid isomeric impurities of Semaglutide using liquid chromatography-high resolution tandem mass spectrometry. J Pharm Biomed Anal. 2023;224:115164. DOI: 10.1016/j.jpba.2022.115164Hong S.Y., Oh J.E., Lee K.H. Effect of D-amino acid substitution on the stability, the secondary structure, and the activity of membrane-active peptide // Biochem Pharmacol. – 1999. – Vol. 58, No. 11. – P. 1775–1780. DOI: 10.1016/s0006-2952(99)00259-2Hong SY, Oh JE, Lee KH. Effect of D-amino acid substitution on the stability, the secondary structure, and the activity of membrane-active peptide. Biochem Pharmacol. 1999; 58(11):1775–80. DOI: 10.1016/s0006-2952(99)00259-2Гурова О.Ю., Фадеев В.В., Малолеткина Е.С. Инъекционная терапия при сахарном диабете 2 типа: существуют ли эффективные способы повышения приверженности лечению? // Сахарный диабет. – 2018. – Т. 21, № 6. – С. 524–533. DOI: 10.14341/DM9603Gurova OY, Fadeev VV, Maloletkina ES. Injectable therapy in type 2 diabetes mellitus: strategies to improve therapeutic adherence. Diabetes mellitus. 2018;21(6):524–33. DOI: 10.14341/DM9603. Russian

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