clinmedКлиническая медицинаClinical Medicine (Russian Journal)0023-21492412-1339ООО «Медицинское информационное агентство»10.30629/0023-2149-2024-102-7-499-509clinmed-878Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESНовый класс препаратов лечения сахарного диабетаNew class of drugs for the treatment of diabetes mellitushttps://orcid.org/0000-0003-4722-7707ИсламоваА. И.IslamovaA. I.

Исламова Аделя Ильдаровна

Уфа

Adeliya I. Islamova 

Ufa

https://orcid.org/0000-0002-4201-4537СабироваА. Р.SabirovaA. R.

Сабирова Адиля Радиковна

Уфа

Adilya R. Sabirova 

Ufa

https://orcid.org/0000-0002-2892-5852БатыршинаЭ. Р.BatyrshinaE. R.

Батыршина Эндже Ривалевна

Уфа

Endje R. Batyrshina 

Ufa

https://orcid.org/0000-0001-8140-9219МузафароваГ. Н.MuzafarovaG. N.

Музафарова Гузалия Насимовна

Уфа

Guzaliya N. Muzafarova 

Ufa

https://orcid.org/0000-0001-9007-4115ХабибуллинаЛ. Х.KhabibullinaL. H.

Хабибуллина Лиана Халиловна

Уфа

Liana H. Khabibullina 

Ufa

https://orcid.org/0000-0001-6257-303XКираеваА. Э.KiraevaA. E.

Кираева Аделина Эдуардовна

Уфа

Adelina E. Kiraeva 

Ufa

https://orcid.org/0000-0003-4690-3267ПятышинаА. В.PyatyshinaA. V.

Кираева Аделина Эдуардовна

Уфа

Anastasiya V. Pyatyshina 

Ufa

https://orcid.org/0000-0002-7764-7369АрслановаЭ. Ф.ArslanovaE. F.

Арсланова Эльвина Филюсовна

Уфа

Elvina F. Arslanova 

Ufa

https://orcid.org/0000-0001-6257-2096ВинниковаА. А.VinnikovaA. A.

Винникова Анастасия Алексеевна

Уфа

Anastasiya A. Vinnikova 

Ufa

https://orcid.org/0000-0003-2741-8565ПисаревА. А.PisarevA. A.

Писарев Андрей Александрович

Уфа

Andrey A. Pisarev 

Ufa

https://orcid.org/0000-0003-2115-9697НабиуллинаА. Ф.NabiullinaA. F.

Набиуллина Амина Фаргатовна

Уфа

Amina F. Nabiullina 

Ufa

https://orcid.org/0000-0002-5940-6369ГимазиеваА. И.Gimazieva A. I.

Гимазиева Алсу Илдусовна

Уфа

Alsu I. Gimazieva 

Ufa

https://orcid.org/0000-0002-2405-1801КузнецовК. О.KuznetsovK. O.

Кузнецов Кирилл Олегович

Уфа

Kirill O. Kuznetsov 

Ufa

kirillkuznetsov@aol.comФГБОУ ВО «Башкирский государственный медицинский университет» Минздрава РоссииРоссияBashkir State Medical University of the Ministry of Health of RussiaRussian Federation2024211120241027499509Copyright © Исламова А.И., Сабирова А.Р., Батыршина Э.Р., Музафарова Г.Н., Хабибуллина Л.Х., Кираева А.Э., Пятышина А.В., Арсланова Э.Ф., Винникова А.А., Писарев А.А., Набиуллина А.Ф., Гимазиева А.И., Кузнецов К.О., 20242024Исламова А.И., Сабирова А.Р., Батыршина Э.Р., Музафарова Г.Н., Хабибуллина Л.Х., Кираева А.Э., Пятышина А.В., Арсланова Э.Ф., Винникова А.А., Писарев А.А., Набиуллина А.Ф., Гимазиева А.И., Кузнецов К.О.Islamova A.I., Sabirova A.R., Batyrshina E.R., Muzafarova G.N., Khabibullina L.H., Kiraeva A.E., Pyatyshina A.V., Arslanova E.F., Vinnikova A.A., Pisarev A.A., Nabiullina A.F., Gimazieva  A.I., Kuznetsov K.O.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.clinmedjournal.com/jour/article/view/878

Сахарный диабет и ожирение являются одними из ключевых проблем для современного здравоохранения. В мире около 425 млн человек с сахарным диабетом, а число с людей с избыточным весом или ожирением составляет более трети от всей человеческой популяции. Это обусловливает необходимость поиска новых терапевтических опций лечения данных заболеваний, усовершенствования существующих схем лечения. В данном актуализирующем обзоре рассматриваются как сами понятия «сахарный диабет» и ожирение, существующие схемы лечения, так и новый класс противодиабетических препаратов — агонисты рецепторов глюкозозависимого инсулинотропного пептида и глюкагоноподобного пептида-1, а также его основной представитель — тирзепатид. Демонстрируются история развития, обоснование механизма действия, а также существующие клинические исследования тирзепатида, ключевого представителя этого развивающегося класса препаратов. Данный препарат продемонстрировал статистически значимое снижение гликозилированного гемоглобина у пациентов с сахарным диабетом, снижение массы тела у пациентов как с ожирением, так и с и/или сахарным диабетом, по сравнению с несколькими классами антидиабетических препаратов. Однако необходимо отметить, что побочные реакции в клинических исследованиях встречались чаще в группе тирзепатида, особенно при высоких дозировках, что подчеркивает необходимость индивидуального подхода при назначении данного препарата. Кроме того, было проведено сравнение лишь с инсулином и агонистами рецепторов глюкагоноподобного пептида-1, что указывает на ограниченную клиническую значимость данных исследований. Возможно, введение тирзепатида в клиническую практику позволит в будущем снизить уровень ожирения, а также контролировать течение сахарного диабета у многих пациентов, что снизит уровень осложнений и смертность от данных состояний.

Diabetes and obesity are among the key issues for modern healthcare. Approximately 425 million people worldwide have diabetes, and the number of individuals with overweight or obesity exceeds one-third of the entire human population. This necessitates the search for new therapeutic options for treating these conditions and the improvement of existing treatment regimens. This review discusses both the concepts of “diabetes” and obesity, existing treatment schemes, and a new class of antidiabetic drugs—glucose-dependent insulinotropic peptide receptor agonists and glucagon-like peptide-1, as well as its main representative—tirzepatide. The review presents the history of development, justification of the mechanism of action, and existing clinical studies on tirzepatide, a key representative of this emerging class of drugs. This medication has demonstrated a statistically significant reduction in glycated hemoglobin in patients with diabetes and weight loss in patients with obesity and/ or diabetes compared to several classes of antidiabetic drugs. However, it should be noted that adverse reactions in clinical studies were more frequent in the tirzepatide group, especially at high doses, highlighting the need for an individualized approach when prescribing this medication. Additionally, comparisons were made only with insulin and glucagon-like peptide-1 receptor agonists, indicating the limited clinical significance of these studies. The introduction of tirzepatide into clinical practice may potentially reduce obesity levels and help control the progression of diabetes in many patients, thereby decreasing complications and mortality associated with these conditions.

сахарный диабетгликозилированный гемоглобинглюкагоноподобный пептид-1глюкозозависимый инсулинотропный пептидтирзепатидdiabetesglycated hemoglobinglucagon-like peptide-1glucose-dependent insulinotropic peptidetirzepatideReferencesChobot A., Górowska-Kowolik K., Sokołowska M., Jarosz-Chobot P. Obesity and diabetes-Not only a simple link between two epidemics. Diabetes Metab. Res. Rev. 2018;34(7):e3042. DOI: 10.1002/dmrr.3042Chobot A., Górowska-Kowolik K., Sokołowska M., Jarosz-Chobot P. Obesity and diabetes-Not only a simple link between two epidemics. Diabetes Metab. Res. Rev. 2018;34(7):e3042. DOI: 10.1002/dmrr.3042Cho N.H., Shaw J.E., Karuranga S. et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res. Clin. Pract. 2018;138:271–281. DOI: 10.1016/j.diabres.2018.02.023Cho N.H., Shaw J.E., Karuranga S. et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res. Clin. Pract. 2018;138:271–281. DOI: 10.1016/j.diabres.2018.02.023Forouhi N.G., Wareham N.J. Epidemiology of diabetes. Medicine (Abingdon). 2014;42(12):698–702. DOI: 10.1016/j.mpmed.2014.09.007Forouhi N.G., Wareham N.J. Epidemiology of diabetes. Medicine (Abingdon). 2014;42(12):698–702. DOI: 10.1016/j.mpmed.2014.09.007Дедов И.И., Шестакова М.В., Викулова О.К., Железнякова А.В., Исаков М.А. Эпидемиологические характеристики сахарного диабета в Российской Федерации: клинико-статистический анализ по данным регистра сахарного диабета на 01.01. 2021. Сахарный диабет. 2021;24(3):204–221.Dedov I.I., Shestakova M.V., Vikulova O.K., Zheleznyakova A.V., Isakov M.A. Epidemiological characteristics of diabetes mellitus in the Russian Federation: clinical and statistical analysis according to the Federal Diabetes Register data of 01.01.2021. Saharnyj diabet. 2021;24(3):204–221. (In Russian)]. DOI: 10.14341/DM12759Chooi Y.C., Ding C., Magkos F. The epidemiology of obesity. Metabolism. 2019;92:6–10. DOI: 10.1016/j.metabol.2018.09.005Chooi Y.C., Ding C., Magkos F. The epidemiology of obesity. Metabolism. 2019;92:6–10. DOI: 10.1016/j.metabol.2018.09.005Dahlén A.D., Dashi G., Maslov I., et al. Trends in Antidiabetic Drug Discovery: FDA Approved Drugs, New Drugs in Clinical Trials and Global Sales. Front Pharmacol. 2022;12:807548. DOI: 10.3389/fphar.2021.807548Dahlén A.D., Dashi G., Maslov I., et al. Trends in Antidiabetic Drug Discovery: FDA Approved Drugs, New Drugs in Clinical Trials and Global Sales. Front Pharmacol. 2022;12:807548. DOI: 10.3389/fphar.2021.807548Syed Y.Y. Tirzepatide: First Approval. Drugs. 2022;82(11):1213– 1220. DOI: 10.1007/s40265-022-01746-8Syed Y.Y. Tirzepatide: First Approval. Drugs. 2022;82(11):1213– 1220. DOI: 10.1007/s40265-022-01746-8Jastreboff A.M., Aronne L.J., Ahmad N.N. et al. Tirzepatide Once Weekly for the Treatment of Obesity. N. Engl. J. Med. 2022;387(3):205–216. DOI: 10.1056/NEJMoa2206038Jastreboff A.M., Aronne L.J., Ahmad N.N. et al. Tirzepatide Once Weekly for the Treatment of Obesity. N. Engl. J. Med. 2022;387(3):205–216. DOI: 10.1056/NEJMoa2206038Chow E., Chan J.C.N. The emerging role of incretins and twincretins. Nat. Rev. Endocrinol. 2022;18(2):73–74. DOI: 10.1038/s41574-021-00607-wChow E., Chan J.C.N. The emerging role of incretins and twincretins. Nat. Rev. Endocrinol. 2022;18(2):73–74. DOI: 10.1038/s41574-021-00607-wSattar N. Advances in the clinical management of type 2 diabetes: a brief history of the past 15 years and challenges for the future. BMC Med. 2019;17(1):46. DOI: 10.1186/s12916-019-1281-1Sattar N. Advances in the clinical management of type 2 diabetes: a brief history of the past 15 years and challenges for the future. BMC Med. 2019;17(1):46. DOI: 10.1186/s12916-019-1281-1Min T., Bain S.C. The role of tirzepatide, dual GIP and GLP-1 receptor agonist, in the management of type 2 diabetes: the SURPASS clinical trials. Diabetes Ther. 2021;12(1):143–157. DOI: 10.1007/s13300-020-00981-0Min T., Bain S.C. The role of tirzepatide, dual GIP and GLP-1 receptor agonist, in the management of type 2 diabetes: the SURPASS clinical trials. Diabetes Ther. 2021;12(1):143–157. DOI: 10.1007/s13300-020-00981-0Day J.W., Ottaway N., Patterson J.T. et al. A new glucagon and GLP-1 co-agonist eliminates obesity in rodents. Nat. Chem. Biol. 2009;5(10):749–757. DOI: 10.1038/nchembio.209Day J.W., Ottaway N., Patterson J.T. et al. A new glucagon and GLP-1 co-agonist eliminates obesity in rodents. Nat. Chem. Biol. 2009;5(10):749–757. DOI: 10.1038/nchembio.209Finan B., Clemmensen C., Müller T.D. Emerging opportunities for the treatment of metabolic diseases: Glucagon-like peptide-1 based multi-agonists. Mol. Cell. Endocrinol. 2015;418(1):42–54. DOI: 10.1016/j.mce.2015.07.003Finan B., Clemmensen C., Müller T.D. Emerging opportunities for the treatment of metabolic diseases: Glucagon-like peptide-1 based multi-agonists. Mol. Cell. Endocrinol. 2015;418(1):42–54. DOI: 10.1016/j.mce.2015.07.003Nauck M.A., Bartels E., Orskov C. et al. Additive insulinotropic eff ects of exogenous synthetic human gastric inhibitory polypeptide and glucagon-like peptide-1-(7-36) amide infused at nearphysiological insulinotropic hormone and glucose concentrations. J. Clin. Endocrinol. Metab. 1993;76(4):912–917. DOI: 10.1210/jcem.76.4.8473405Nauck M.A., Bartels E., Orskov C. et al. Additive insulinotropic eff ects of exogenous synthetic human gastric inhibitory polypeptide and glucagon-like peptide-1-(7-36) amide infused at nearphysiological insulinotropic hormone and glucose concentrations. J. Clin. Endocrinol. Metab. 1993;76(4):912–917. DOI: 10.1210/jcem.76.4.8473405Gasbjerg L.S., Bergmann N.C., Stensen S. et al. Evaluation of the incretin eff ect in humans using GIP and GLP-1 receptor antagonists. Peptides. 2020;125:170183. DOI: 10.1016/j.peptides.2019.170183Gasbjerg L.S., Bergmann N.C., Stensen S. et al. Evaluation of the incretin eff ect in humans using GIP and GLP-1 receptor antagonists. Peptides. 2020;125:170183. DOI: 10.1016/j.peptides.2019.170183Nauck M.A., Meier J.J. Incretin hormones: Their role in health and disease. Diabetes Obes. Metab. 2018;20(1):5–21. DOI: 10.1111/dom.13129Nauck M.A., Meier J.J. Incretin hormones: Their role in health and disease. Diabetes Obes. Metab. 2018;20(1):5–21. DOI: 10.1111/dom.13129Gallwitz B., Witt M., Fölsch U.R., Creutzfeldt W., Schmidt W.E. Binding specifi city and signal transduction of receptors for glucagonlike peptide-1(7-36) amide and gastric inhibitory polypeptide on RINm5F insulinoma cells. J. Mol. Endocrinol. 1993;10(3):259–268. DOI: 10.1677/jme.0.0100259Gallwitz B., Witt M., Fölsch U.R., Creutzfeldt W., Schmidt W.E. Binding specifi city and signal transduction of receptors for glucagonlike peptide-1(7-36) amide and gastric inhibitory polypeptide on RINm5F insulinoma cells. J. Mol. Endocrinol. 1993;10(3):259–268. DOI: 10.1677/jme.0.0100259Finan B., Ma T., Ottaway N. et al. Unimolecular dual incretins maximize metabolic benefi ts in rodents, monkeys, and humans. Sci. Transl. Med. 2013;5(209):209ra151. DOI: 10.1126/scitranslmed.3007218Finan B., Ma T., Ottaway N. et al. Unimolecular dual incretins maximize metabolic benefi ts in rodents, monkeys, and humans. Sci. Transl. Med. 2013;5(209):209ra151. DOI: 10.1126/scitranslmed.3007218Harrison C. Obesity and diabetes: Two-for-one strike at incretins. Nat. Rev. Drug Discov. 2014;13(1):18–19. DOI: 10.1038/nrd4208Harrison C. Obesity and diabetes: Two-for-one strike at incretins. Nat. Rev. Drug Discov. 2014;13(1):18–19. DOI: 10.1038/nrd4208Nørregaard P.K., Deryabina M.A., Tofteng Sh.P. et al. A novel GIP analogue, ZP4165, enhances glucagon-like peptide-1-induced body weight loss and improves glycaemic control in rodents. Diabetes Obes. Metab. 2018;20(1):60–68. DOI: 10.1111/dom.13034Nørregaard P.K., Deryabina M.A., Tofteng Sh.P. et al. A novel GIP analogue, ZP4165, enhances glucagon-like peptide-1-induced body weight loss and improves glycaemic control in rodents. Diabetes Obes. Metab. 2018;20(1):60–68. DOI: 10.1111/dom.13034Samms R.J., Coghlan M.P., Sloop K.W. How may GIP enhance the therapeutic effi cacy of GLP-1? Trends Endocrinol. Metab. 2020;31(6):410–421. DOI: 10.1016/j.tem.2020.02.006Samms R.J., Coghlan M.P., Sloop K.W. How may GIP enhance the therapeutic effi cacy of GLP-1? Trends Endocrinol. Metab. 2020;31(6):410–421. DOI: 10.1016/j.tem.2020.02.006Knerr P.J., Mowery S.A., Douros JD. et al. Next generation GLP-1/GIP/glucagon triple agonists normalize body weight in obese mice. Mol. Metab. 2022;63:101533. DOI: 10.1016/j.molmet.2022.101533Knerr P.J., Mowery S.A., Douros JD. et al. Next generation GLP-1/GIP/glucagon triple agonists normalize body weight in obese mice. Mol. Metab. 2022;63:101533. DOI: 10.1016/j.molmet.2022.101533Chavda V.P., Ajabiya J., Teli D., Bojarska J., Apostolopoulos V. Tirzepatide, a new era of dual-targeted treatment for diabetes and obesity: a mini-review. Molecules. 2022;27(13):4315. DOI: 10.3390/molecules27134315Chavda V.P., Ajabiya J., Teli D., Bojarska J., Apostolopoulos V. Tirzepatide, a new era of dual-targeted treatment for diabetes and obesity: a mini-review. Molecules. 2022;27(13):4315. DOI: 10.3390/molecules27134315Orme M.E., Nguyen H., Lu J.Y. et al. Comparative eff ectiveness of glycemic control in patients with type 2 diabetes treated with GLP-1 receptor agonists: a network meta-analysis of placebo-controlled and active-comparator trials. Diabetes Metab. Syndr. Obes. 2017;10:111–122. Published 2017 Mar 29. DOI: 10.2147/DMSO.S116810Orme M.E., Nguyen H., Lu J.Y. et al. Comparative eff ectiveness of glycemic control in patients with type 2 diabetes treated with GLP-1 receptor agonists: a network meta-analysis of placebo-controlled and active-comparator trials. Diabetes Metab. Syndr. Obes. 2017;10:111–122. Published 2017 Mar 29. DOI: 10.2147/DMSO.S116810Coskun T., Sloop K.W., Loghin C. et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Mol. Metab. 2018;18:3–14. DOI: 10.1016/j.molmet.2018.09.009Coskun T., Sloop K.W., Loghin C. et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Mol. Metab. 2018;18:3–14. DOI: 10.1016/j.molmet.2018.09.009Дружилов М.А., Кузнецова Т.Ю., Чумакова Г.А. Мультиагонисты “инкретиновой оси” как перспективный инструмент управления кардиометаболическим риском при синдроме висцерального ожирения. Российский кардиологический журнал. 2022;27(4):4755.Druzhilov M.A., Kuznetsova T.Y., Chumakova G.A. Multiagonists of the “incretin axis” as a promising tool for managing cardiometabolic risk in visceral obesity. Rossijskij kardiologicheskij zhurnal. 2022;27(4):4755. (In Russian)] DOI: 10.15829/1560-4071-2022-4755fda.gov [Internet]. U.S. Food and Drug Administration; MOUNJARO. MOUNJAROTM (tirzepatide) Injection, for subcutaneous use [updated 2022 May 13; cited 2022 Nov 3]. [Electronic resource]. URL: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215866s000lbl.pdffda.gov [Internet]. U.S. Food and Drug Administration; MOUNJARO. MOUNJAROTM (tirzepatide) Injection, for subcutaneous use [updated 2022 May 13; cited 2022 Nov 3]. [Electronic resource]. URL: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215866s000lbl.pdfУсеинова А.Н., Егорова Е.А., Елишева Е.А., Бейтуллаев А.М., Корянова К.Н. Основные направления и перспективы в терапии синдрома поликистоза яичников. Сибирский научный медицинский журнал. 2021;41(6):18–29.Useinova A.N., Egorova E.A., Yelisheva E.A., Beitullaev А.М., Koryanova K.N. The main directions and prospects in polycystic ovary syndrome treatment. Sibirskiy nauchnyy meditsinskiy zhurnal. 2021;41(6):18–29. (In Russian)]. DOI: 10.18699/SSMJ20210602Rosenstock J., Wysham C., Frías J.P. et al. Effi cacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial [published correction appears in Lancet. 2021 Jul 17;398(10296):212]. Lancet. 2021;398(10295):143–155. DOI: 10.1016/S0140-6736(21)01324-6Rosenstock J., Wysham C., Frías J.P. et al. Effi cacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial [published correction appears in Lancet. 2021 Jul 17;398(10296):212]. Lancet. 2021;398(10295):143–155. DOI: 10.1016/S0140-6736(21)01324-6Frías J.P., Davies M.J., Rosenstock J. et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N. Engl. J. Med. 2021;385(6):503–515. DOI: 10.1056/NEJMoa2107519Frías J.P., Davies M.J., Rosenstock J. et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N. Engl. J. Med. 2021;385(6):503–515. DOI: 10.1056/NEJMoa2107519Ludvik B., Giorgino F., Jódar E. et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 2021;398(10300):583–598. DOI: 10.1016/S0140-6736(21)01443-4Ludvik B., Giorgino F., Jódar E. et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 2021;398(10300):583–598. DOI: 10.1016/S0140-6736(21)01443-4Del Prato S., Kahn S.E., Pavo I. et al. 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):1811–1824. DOI: 10.1016/S0140-6736(21)02188-7Del Prato S., Kahn S.E., Pavo I. et al. 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):1811–1824. DOI: 10.1016/S0140-6736(21)02188-7Dahl D., Onishi Y., Norwood P. et al. Eff ect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial. JAMA. 2022;327(6):534–545. DOI: 10.1001/jama.2022.0078Dahl D., Onishi Y., Norwood P. et al. Eff ect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial. JAMA. 2022;327(6):534–545. DOI: 10.1001/jama.2022.0078National Library of Medicine (U.S.). (2020, October). A Study of Tirzepatide (LY3298176) Versus Insulin Lispro (U100) in Participants With Type 2 Diabetes Inadequately Controlled on Insulin Glargine (U100) With or Without Metformin (SURPASS-6). Identifi er NCT04537923. [updated 2021 Oct 19; cited 2022 Nov 3]. [Electronic resource]. URL: https://clinicaltrials.gov/ct2/show/NCT04537923National Library of Medicine (U.S.). (2020, October). A Study of Tirzepatide (LY3298176) Versus Insulin Lispro (U100) in Participants With Type 2 Diabetes Inadequately Controlled on Insulin Glargine (U100) With or Without Metformin (SURPASS-6). Identifi er NCT04537923. [updated 2021 Oct 19; cited 2022 Nov 3]. [Electronic resource]. URL: https://clinicaltrials.gov/ct2/show/NCT04537923National Library of Medicine (U.S.). (2022, April). A Study to Evaluate Tirzepatide (LY3298176) in Pediatric and Adolescent Participants With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin or Basal Insulin or Both (SURPASS-PEDS). Identifi er NCT05260021. [updated 2022 Oct 20; cited 2022 Nov 3]. [Electronic resource]. URL: https://clinicaltrials.gov/ct2/show/NCT05260021National Library of Medicine (U.S.). (2022, April). A Study to Evaluate Tirzepatide (LY3298176) in Pediatric and Adolescent Participants With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin or Basal Insulin or Both (SURPASS-PEDS). Identifi er NCT05260021. [updated 2022 Oct 20; cited 2022 Nov 3]. [Electronic resource]. URL: https://clinicaltrials.gov/ct2/show/NCT05260021National Library of Medicine (U.S.). (2019, December — 2021, November). A study of Tirzepatide (LY3298176) in participants with type 2 diabetes on metformin with or without sulfonylurea (surpassAP-combo). Identifi er NCT04093752. [updated 2021 Dec 14; cited 2022 Nov 3]. [Electronic resource]. URL: https://clinicaltrials.gov/ct2/show/NCT04093752National Library of Medicine (U.S.). (2019, December — 2021, November). A study of Tirzepatide (LY3298176) in participants with type 2 diabetes on metformin with or without sulfonylurea (surpassAP-combo). Identifi er NCT04093752. [updated 2021 Dec 14; cited 2022 Nov 3]. [Electronic resource]. URL: https://clinicaltrials.gov/ct2/show/NCT04093752Inagaki N., Takeuchi M., Oura T. et al. Efficacy and safety of tirzepatide monotherapy compared with dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono): a double-blind, multicentre, randomised, phase 3 trial. Lancet Diabetes Endocrinol. 2022;10(9):623–633. DOI: 10.1016/S2213-8587(22)00188-7Inagaki N., Takeuchi M., Oura T. et al. Efficacy and safety of tirzepatide monotherapy compared with dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono): a double-blind, multicentre, randomised, phase 3 trial. Lancet Diabetes Endocrinol. 2022;10(9):623–633. DOI: 10.1016/S2213-8587(22)00188-7Kadowaki T., Chin R., Ozeki A., Imaoka T., Ogawa Y. Safety and effi cacy of tirzepatide as an add-on to single oral antihyperglycaemic medication in patients with type 2 diabetes in Japan (SURPASS J-combo): a multicentre, randomised, open-label, parallel-group, phase 3 trial. Lancet Diabetes Endocrinol. 2022;10(9):634–644. DOI: 10.1016/S2213-8587(22)00187-5Kadowaki T., Chin R., Ozeki A., Imaoka T., Ogawa Y. Safety and effi cacy of tirzepatide as an add-on to single oral antihyperglycaemic medication in patients with type 2 diabetes in Japan (SURPASS J-combo): a multicentre, randomised, open-label, parallel-group, phase 3 trial. Lancet Diabetes Endocrinol. 2022;10(9):634–644. DOI: 10.1016/S2213-8587(22)00187-5National Library of Medicine (U.S.). (2020, May — 2024, October). A Study of Tirzepatide (LY3298176) Compared With Dulaglutide on Major Cardiovascular Events in Participants With Type 2 Diabetes (SURPASS-CVOT). Identifi er NCT04255433. [updated 2022 Dec 12; cited 2022 Dec 21]. [Electronic resource]. URL: https://clinicaltrials.gov/ct2/show/NCT04255433National Library of Medicine (U.S.). (2020, May — 2024, October). A Study of Tirzepatide (LY3298176) Compared With Dulaglutide on Major Cardiovascular Events in Participants With Type 2 Diabetes (SURPASS-CVOT). Identifi er NCT04255433. [updated 2022 Dec 12; cited 2022 Dec 21]. [Electronic resource]. URL: https://clinicaltrials.gov/ct2/show/NCT04255433Jastreboff A.M., Aronne L.J., Ahmad N.N. et al. Tirzepatide once weekly for the treatment of obesity. N. Engl. J. Med. 2022;387(3):205–216. DOI: 10.1056/NEJMoa2206038Jastreboff A.M., Aronne L.J., Ahmad N.N. et al. Tirzepatide once weekly for the treatment of obesity. N. Engl. J. Med. 2022;387(3):205–216. DOI: 10.1056/NEJMoa2206038National Library of Medicine (U.S.). (2021, March). A study of tirzepatide (ly3298176) in participants with type 2 diabetes who have obesity or are overweight (SURMOUNT-2). Identifi er NCT04657003. [updated 2022 Apr 19; cited 2022 Nov 3]. [Electronic resource]. URL: https://clinicaltrials.gov/ct2/show/NCT04657003National Library of Medicine (U.S.). (2021, March). A study of tirzepatide (ly3298176) in participants with type 2 diabetes who have obesity or are overweight (SURMOUNT-2). Identifi er NCT04657003. [updated 2022 Apr 19; cited 2022 Nov 3]. [Electronic resource]. URL: https://clinicaltrials.gov/ct2/show/NCT04657003National Library of Medicine (U.S.). (2021, March). A study of tirzepatide (ly3298176) in participants after a lifestyle weight loss program (SURMOUNT-3). Identifi er NCT04657016. [updated 2022 Mar 23; cited 2022 Nov 3]. [Electronic resource]. URL: https://clinicaltrials.gov/ct2/show/NCT04657016National Library of Medicine (U.S.). (2021, March). A study of tirzepatide (ly3298176) in participants after a lifestyle weight loss program (SURMOUNT-3). Identifi er NCT04657016. [updated 2022 Mar 23; cited 2022 Nov 3]. [Electronic resource]. URL: https://clinicaltrials.gov/ct2/show/NCT04657016National Library of Medicine (U.S.). (2021, March). A study of tirzepatide (ly3298176) in participants with obesity or overweight for the maintenance of weight loss (SURMOUNT-4). Identifi er NCT04660643. [updated 2022 Oct 6; cited 2022 Nov 3]. [Electronic resource]. URL: https://clinicaltrials.gov/ct2/show/NCT04660643National Library of Medicine (U.S.). (2021, March). A study of tirzepatide (ly3298176) in participants with obesity or overweight for the maintenance of weight loss (SURMOUNT-4). Identifi er NCT04660643. [updated 2022 Oct 6; cited 2022 Nov 3]. [Electronic resource]. URL: https://clinicaltrials.gov/ct2/show/NCT04660643National Library of Medicine (U.S.). (2021, September). A study of tirzepatide (LY3298176) in chinese participants without type 2 diabetes who have obesity or overweight (SURMOUNT-CN). Identifi er NCT05024032. [updated 2022 Oct 18; cited 2022 Nov 3]. [Electronic resource]. URL: https://clinicaltrials.gov/ct2/show/NCT05024032National Library of Medicine (U.S.). (2021, September). A study of tirzepatide (LY3298176) in chinese participants without type 2 diabetes who have obesity or overweight (SURMOUNT-CN). Identifi er NCT05024032. [updated 2022 Oct 18; cited 2022 Nov 3]. [Electronic resource]. URL: https://clinicaltrials.gov/ct2/show/NCT05024032National Library of Medicine (U.S.). (2021, May). A study of tirzepatide (LY3298176) in participants with obesity disease (SURMOUNT-J). Identifi er NCT04844918. [updated 2022 Feb 7; cited 2022 Nov 3]. [Electronic resource]. URL: https://www.clinicaltrials.gov/ct2/show/NCT04844918National Library of Medicine (U.S.). (2021, May). A study of tirzepatide (LY3298176) in participants with obesity disease (SURMOUNT-J). Identifi er NCT04844918. [updated 2022 Feb 7; cited 2022 Nov 3]. [Electronic resource]. URL: https://www.clinicaltrials.gov/ct2/show/NCT04844918National Library of Medicine (U.S.). (2022, June). Obstructive Sleep Apnea Master Protocol GPIF: A Study of Tirzepatide (LY3298176) in Participants With Obstructive Sleep Apnea (SURMOUNT-OSA). Identifi er NCT05412004. [updated 2022 Oct 19; cited 2022 Nov 3]. [Electronic resource]. URL: https://clinicaltrials.gov/ct2/show/study/NCT05412004National Library of Medicine (U.S.). (2022, June). Obstructive Sleep Apnea Master Protocol GPIF: A Study of Tirzepatide (LY3298176) in Participants With Obstructive Sleep Apnea (SURMOUNT-OSA). Identifi er NCT05412004. [updated 2022 Oct 19; cited 2022 Nov 3]. [Electronic resource]. URL: https://clinicaltrials.gov/ct2/show/study/NCT05412004National Library of Medicine (U.S.). (2021, April). A study of tirzepatide (LY3298176) in participants with heart failure with preserved ejection fraction and obesity (SUMMIT). Identifi er NCT04847557. [updated 2022 Oct 20; cited 2022 Nov 3]. [Electronic resource]. URL: https://clinicaltrials.gov/ct2/show/NCT04847557National Library of Medicine (U.S.). (2021, April). A study of tirzepatide (LY3298176) in participants with heart failure with preserved ejection fraction and obesity (SUMMIT). Identifi er NCT04847557. [updated 2022 Oct 20; cited 2022 Nov 3]. [Electronic resource]. URL: https://clinicaltrials.gov/ct2/show/NCT04847557Frias J.P., Nauck M.A., Van J. et al. Effi cacy and tolerability of tirzepatide, a dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist in patients with type 2 diabetes: A 12-week, randomized, double-blind, placebo-controlled study to evaluate diff erent dose-escalation regimens. Diabetes Obes. Metab. 2020;22(6):938–946. DOI: 10.1111/dom.13979Frias J.P., Nauck M.A., Van J. et al. Effi cacy and tolerability of tirzepatide, a dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist in patients with type 2 diabetes: A 12-week, randomized, double-blind, placebo-controlled study to evaluate diff erent dose-escalation regimens. Diabetes Obes. Metab. 2020;22(6):938–946. DOI: 10.1111/dom.13979Frias J.P., Nauck M.A., Van J. et al. Effi cacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparatorcontrolled phase 2 trial. Lancet. 2018;392(10160):2180–2193. DOI:10.1016/S0140-6736(18)32260-8Frias J.P., Nauck M.A., Van J. et al. Effi cacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparatorcontrolled phase 2 trial. Lancet. 2018;392(10160):2180–2193. DOI:10.1016/S0140-6736(18)32260-8National Library of Medicine (U.S.). (2019, November). A study of tirzepatide (LY3298176) in participants with nonalcoholic steatohepatitis (NASH) (SYNERGY-NASH). Identifi er NCT04166773. [updated 2022 Oct 20; cited 2022 Nov 3]. [Electronic resource]. URL: https://clinicaltrials.gov/ct2/show/NCT04166773National Library of Medicine (U.S.). (2019, November). A study of tirzepatide (LY3298176) in participants with nonalcoholic steatohepatitis (NASH) (SYNERGY-NASH). Identifi er NCT04166773. [updated 2022 Oct 20; cited 2022 Nov 3]. [Electronic resource]. URL: https://clinicaltrials.gov/ct2/show/NCT04166773Jung H.N., Jung C.H. The upcoming weekly tides (Semaglutide vs. Tirzepatide) against obesity: STEP or SURPASS? J. Obes. Metab. Syndr. 2022;31(1):28–36. DOI: 10.7570/jomes22012Jung H.N., Jung C.H. The upcoming weekly tides (Semaglutide vs. Tirzepatide) against obesity: STEP or SURPASS? J. Obes. Metab. Syndr. 2022;31(1):28–36. DOI: 10.7570/jomes22012Аметов А.С. Уровень гликированного гемоглобина как значимый маркер полноценного гликемического контроля и предиктор поздних сосудистых осложнений сахарного диабета 2 типа. РМЖ. 2011;13:832.Ametov A.S. The level of glycated hemoglobin as a signifi cant marker of complete glycemic control and a predictor of late vascular complications of type 2 diabetes mellitus. RMZH. 2011;13:832. (In Russian)].American Diabetes Association Professional Practice Committee, Draznin B, Aroda VR, et al. 6. Glycemic Targets: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2022;45(1):S83–S96. DOI: 10.2337/dc22-S006American Diabetes Association Professional Practice Committee, Draznin B, Aroda VR, et al. 6. Glycemic Targets: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2022;45(1):S83–S96. DOI: 10.2337/dc22-S006Dutta D., Surana V., Singla R. et al. Effi cacy and safety of novel twincretin tirzepatide a dual GIP and GLP-1 receptor agonist in the management of type-2 diabetes: A Cochrane meta-analysis. Indian J. Endocrinol. Metab. 2021;25(6):475–489. DOI: 10.4103/ijem.ijem_423_21Dutta D., Surana V., Singla R. et al. Effi cacy and safety of novel twincretin tirzepatide a dual GIP and GLP-1 receptor agonist in the management of type-2 diabetes: A Cochrane meta-analysis. Indian J. Endocrinol. Metab. 2021;25(6):475–489. DOI: 10.4103/ijem.ijem_423_21Karagiannis T., Avgerinos I., Liakos A. et al. Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis. Diabetologia. 2022;65(8):1251–1261. DOI: 10.1007/s00125-022-05715-4Karagiannis T., Avgerinos I., Liakos A. et al. Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis. Diabetologia. 2022;65(8):1251–1261. DOI: 10.1007/s00125-022-05715-4Bhagavathula A.S., Vidyasagar K., Tesfaye W. Efficacy and Safety of Tirzepatide in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Phase II/III Trials. Pharmaceuticals (Basel). 2021;14(10):991. DOI: 10.3390/ph14100991Bhagavathula A.S., Vidyasagar K., Tesfaye W. Efficacy and Safety of Tirzepatide in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Phase II/III Trials. Pharmaceuticals (Basel). 2021;14(10):991. DOI: 10.3390/ph14100991

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