New horizons in the management of metabolic diseases: Focus on the efficacy and safety of tirzepatide
https://doi.org/10.62751/2713-0177-2025-6-3-03
Abstract
Type 2 diabetes mellitus (T2DM) and obesity are two of the most common metabolic pandemics in the modern world. They have a significant impact on the incidence, mortality, and quality of life of populations. Currently, one of the promising pathogenetic mechanisms for metabolic disorders is a defect in incretin response. This defect is observed not only in T2DM, but also in obesity. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are the main incretins that exert systemic regulatory effects on various organs and systems. These peptides have a number of characteristics that determine their physiological effects and therapeutic potential. The last decades have seen the development and introduction of innovative incretin-based sugar-lowering medications, among which tirzepatide occupies a special place. It is the first dual agonist for GLP-1 and GIP receptors to be approved in May 2022, marking the beginning of a new era in treating metabolic diseases. Informally known as twinkretin, this drug demonstrates outstanding efficacy in both glycemic management and weight loss, making it an effective tool for integrated treatment of T2DM and obesity, as well as reducing cardiometabolic risk factors
About the Authors
T. Yu. Demidova
Pirogov Russian National Research Medical University
Russian Federation
Russian Federation
Tatyana Yu. Demidova – D. Sci. (Med.), Prof., Head of the Department of endocrinology, institute of clinical medicine
Scopus Author ID: 7003771623
Moscow
M. Ya. Izmailovа
Pirogov Russian National Research Medical University
Russian Federation
Russian Federation
Maryam Ya. Izmailovа – assistant at the Department of endocrinology, Institute of Clinical Medicine
Moscow
References
1. Duncan BB, Magliano DJ, Boyko EJ. IDF diabetes atlas 11th edition 2025: Global prevalence and projections for 2050. Nephrol Dial Transplant. 2025:gfaf177. doi: 10.1093/ndt/gfaf177.
2. Chandrasekaran P, Weiskirchen R. The role of obesity in type 2 diabetes mellitus-an overview. Int J Mol Sci. 2024;25(3):1882. doi: 10.3390/ijms25031882.
3. Ahren B. DPP-4 inhibition and the path to clinical proof. Front Endocrinol (Lausanne). 2019;10:376. doi: 10.3389/fendo.2019.00376.
4. Nauck M.A., Meier J.J. Incretin hormones: Their role in health and disease. Diabetes Obes. Metab. 2018;20(Suppl. S1):5–21. doi: 10.1111/dom.13129.
5. Yang J, Gu Y, Chen H, Wang H, Hong L, Li B, Yang L. Tirzepatide's innovative applications in the management of type 2 diabetes and its future prospects in cardiovascular health. Front Pharmacol. 2024;15:1453825. doi: 10.3389/fphar.2024.1453825.
6. Muzurovic EM, Volcansek S, Tomsic KZ, Janez A, Mikhailidis DP, Rizzo M et al. Glucagon-like peptide-1 receptor agonists and dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists in the treatment of obesity/metabolic syndrome, prediabetes/diabetes and nonalcoholic fatty liver disease-current evidence. J Cardiovasc Pharmacol Ther. 2022;27:10742484221146371. doi: 10742484221146371.
7. Drucker DJ. The cardiovascular biology of glucagon-like peptide-1. Cell Metab. 2016;24(1):15–30. doi: 10.1016/j.cmet.2016.06.009.
8. Kristensen SL, Rorth R, Jhund PS, Docherty KF, Sattar N, Preiss D et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: A systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019;7(10):776–85. doi: 10.1016/S2213-8587(19)30249-9.
9. Adriaenssens AE, Biggs EK, Darwish T, Tadross J, Sukthankar T, Girish M et al. Glucose-dependent insulinotropic polypeptide receptor-expressing cells in the hypothalamus regulate food intake. Cell Metab. 2019;30(5):987–96.e6. doi: 10.1016/j.cmet.2019.07.013.
10. Tan Q, Akindehin SE, Orsso CE, Waldner RC, DiMarchi RD, Muller TD et al. Recent advances in incretin-based pharmacotherapies for the treatment of obesity and diabetes. Front Endocrinol (Lausanne). 2022;13:838410. doi: 10.3389/fendo.2022.838410.
11. Yu X, Chen S, Funcke JB, Straub LG, Pirro V, Emont MP et al. The GIP receptor activates futile calcium cycling in white adipose tissue to increase energy expenditure and drive weight loss in mice. Cell Metab. 2025;37(1):187–204.e7. doi: 10.1016/j.cmet.2024.11.003.
12. Liu QK. Mechanisms of action and therapeutic applications of GLP-1 and dual GIP/GLP-1 receptor agonists. Front Endocrinol (Lausanne). 2024;15:1431292. doi: 10.3389/fendo.2024.1431292.
13. Heimburger SM, Bergmann NC, Augustin R, Gasbjerg LS, Christensen MB, Knop FK. Glucose-dependent insulinotropic polypeptide (GIP) and cardiovascular disease. Peptides. 2020;125:170174. doi: 10.1016/j.peptides.2019.170174.
14. Gasbjerg LS, Helsted MM, Hartmann B, Jensen MH, Gabe MBN et al. Separate and combined glucometabolic effects of endogenous glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 in healthy individuals. Diabetes. 2019;68(5):906–17. doi: 10.2337/db18-1123.
15. Fisman EZ, Tenenbaum A. The dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide: A novel cardiometabolic therapeutic prospect. Cardiovasc Diabetol. 2021;20(1):225. doi: 10.1186/s12933-021-01412-5.
16. Michałowska J, Miller-Kasprzak E, Bogdanski P. Incretin hormones in obesity and related cardiometabolic disorders: The clinical perspective. Nutrients. 2021;13(2):351. doi: 10.3390/nu13020351.
17. Psaltis JP, Marathe JA, Nguyen MT, Le R, Bursill CA, Marathe CS et al. Incretinbased therapies for the management of cardiometabolic disease in the clinic: Past, present, and future. Med Res Rev. 2025;45(1):29–65. doi: 10.1002/med.22070.
18. Rosenstock J, Wysham C, Frias JP, Kaneko S, Lee CJ, Fernandez Lando L et al. Efficacy 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. Lancet. 2021;398(10295):143–55. doi: 10.1016/S0140-6736(21)01324-6.
19. Frias JP, Davies MJ, Rosenstock J, Perez Manghi FC, Fernandez Lando L, Bergman BK et al.; SURPASS-2 Investigators. Tirzepatide versus semaglutideonce weekly in patients with type 2 diabetes. N Engl J Med. 2021;385(6):503–15. doi: 10.1056/NEJMoa2107519.
20. Ludvik B, Giorgino F, Jodar E, Frias JP, Fernandez Lando L, Brown K 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):583–98. doi: 10.1016/S0140-6736(21)01443-4.
21. Del Prato S, Kahn SE, Pavo I, Weerakkody GJ, Yang Z, Doupis J 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):1811–24. doi: 10.1016/S0140-6736(21)02188-7.
22. Dahl D, Onishi Y, Norwood P, Huh R, Bray R, Patel H et al. Effect 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):534–45. doi: 10.1001/jama.2022.0078.
23. Inagaki N, Takeuchi M, Oura T, Imaoka T, Seino Y. 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):623–33. doi: 10.1016/S2213-8587(22)00188-7.
24. Kadowaki T, Chin R, Ozeki A, Imaoka T, Ogawa Y. Safety and efficacy 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):634–44. doi: 10.1016/S2213-8587(22)00187-5.
25. Zeitler P, Galindo RJ, Davies MJ, Bergman BK, Thieu VT, Nicolay C et al. Earlyonset type 2 diabetes and tirzepatide treatment: A post hoc analysis from the SURPASS clinical trial program. Diabetes Care. 2024;47(6):1056–64. doi: 10.2337/dc23-2356.
26. Sattar N, McGuire DK, Pavo I, Weerakkody GJ, Nishiyama H, Wiese RJ et al. Tirzepatide cardiovascular event risk assessment: A pre-specified meta-analysis. Nat Med. 2022;28(3):591–98. doi: 10.1038/s41591-022-01707-4.
27. Hamza M, Papamargaritis D, Davies MJ. Tirzepatide for overweight and obesity management. Expert Opin Pharmacother. 2025;26(1):31–49. doi: 10.1080/14656566.2024.2436595.
28. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B et al. Tirzepatide once weekly for the treatment of obesity. N Engl J. Med. 2022;387(3):205–16. doi: 10.1056/NEJMoa2206038.
29. Garvey WT, Frias JP, Jastreboff AM, le Roux CW, Sattar N, Aizenberg D et al.; SURMOUNT-2 investigators. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): A double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2023;402(10402):613–26. doi: 10.1016/S0140-6736(23)01200-X.
30. Wadden TA, Chao AM, Machineni S, Kushner R, Ard J, Srivastava G et al. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: The SURMOUNT-3 phase 3 trial. Nat Med. 2023;29(11):2909–18. doi: 10.1038/s41591-023-02597-w.
31. Aronne LJ, Sattar N, Horn DB, Bays HE, Wharton S, Lin WY et al.; SURMOUNT-4 Investigators. Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: The SURMOUNT-4 randomized clinical trial. JAMA. 2024;331(1):38–48. doi: 10.1001/jama.2023.24945.
32. Aronne LJ, Horn DB, le Roux CW, Ho W, Falcon BL, Gomez Valderas E et al.; SURMOUNT-5 Trial Investigators. Tirzepatide as compared with semaglutide for the treatment of obesity. N Engl J Med. 2025;393(1):26–36. doi: 10.1056/NEJMoa2416394.
33. Луговик И.А., Бабина А.В., Арутюнян С.С., Ермолаева Д.О., Сапарова В.Б., Кобелева Т.Н. с соавт. Первый дженерик тирзепатида GP30931: физико-химическое и биологическое сходство с референтным лекарственным средством. Разработка и регистрация лекарственных средств. 2025;14(2):54–74. doi: 10.33380/2305-2066-2025-14-2-2084
Review
For citations:
Demidova T.Yu., Izmailovа M.Ya. New horizons in the management of metabolic diseases: Focus on the efficacy and safety of tirzepatide. FOCUS. Endocrinology. 2025;6(3):12-23. (In Russ.) https://doi.org/10.62751/2713-0177-2025-6-3-03
Views:
384
JATS XML
Email this article 