Неалкогольная жировая болезнь печени: современные подходы к терапии и возможности применения тирзепатида

Введение. В обзоре освещены эпидемиология, патогенез, клиника, диагностика, а также лечение полисиндромной неалкогольной жировой болезни печени (НАЖБП), ассоциированной с ожирением, сахарным диабетом 2-го типа и кардиоваскулярной патологией.

Цель. Оценить у пациентов ключевые патогенетические звенья кардио-рено-гепато-метаболического синдрома, а также терапевтическую эффективность препаратов двойного инкретинового действия, таких как тирзепатид и его отечественный аналог.

Материалы и методы. Поиск литературных источников проводился по базам данных PubMed и Google Scholar. Отбор публикаций проводился по принципу открытого свободного доступа, по анализу аннотаций и оценке релевантности.

Результаты. Для обзора были отобраны 60 статей: 5 русскоязычных и 55 иностранных источников. В большинстве публикаций отражено нарастание глобального бремени НАЖБП из-за роста заболеваемости СД 2-го типа и ожирения, в фармакологической коррекции которых наибольший эффект демонстрируют двойные агонисты глюкагоноподобного пептида-1 (ГПП-1) и глюкозозависимого инсулинотропного полипептида (ГИП), такие как тирзепатид и его российский аналог, эффективные для снижения веса, регрессии фиброза и разрешения неалкогольного стеатогепатита (НAСГ), а также для комплексного лечения хронических метаболических заболеваний за пределами традиционного лечения диабета.

Выводы. На основании большого количества клинических исследований в обзоре оценены возможности амбулаторной медикаментозной терапии НАЖБП, ориентированной на применение агонистов ГПП-1 и ГИП, а также доступных фармакологических препаратов с двойным механизмом действия ГПП-1/ГИП – тирзепатида и его отечественного аналога. При этом последний демонстрирует отчетливое воздействие на патогенную метаболическую дисрегуляцию, воспаление и фиброз.

1. Dezan MGF, Oliveira CP, Cotrim HP. Metabolic dysfunction-associated steatotic liver disease: update. Arq Gastroenterol. 2025;62:e24117. https://doi.org/10.1590/S0004-2803.24612025-117.

2. EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol. 2024;81(3):492–542. https://doi.org/10.1016/j.jhep.2024.04.031.

3. Petta S, Kim K, Targher G, Romeo S, Sookoian S, Zheng MH et al. Focus on semaglutide 2.4 mg/week for the treatment of metabolic dysfunctionassociated steatohepatitis. Liver Int. 2025;45(11):e70407. https://doi.org/10.1111/liv.70407.

4. Choi S, Jung JS, Seo YS, Song S, Ham J, Chung H et al. Convergent metabolic pathways in MASH therapeutics: an AMPK-centric analysis. J Cell Mol Med. 2026;30(2):e71023. https://doi.org/10.1111/jcmm.71023.

5. Amini-Salehi E, Letafatkar N, Norouzi N, Joukar F, Habibi A, Javid M et al. Global Prevalence of Nonalcoholic Fatty Liver Disease: An Updated Review Meta-Analysis comprising a Population of 78 million from 38 Countries. Arch Med Res. 2024;55(6):103043. https://doi.org/10.1016/j.arcmed.2024.103043.

6. Khalifa O, Arredouani A. GLP-1 RAs for treating metabolic dysfunctionassociated steatosis liver disease: from GLP-1 discovery to FDA approval: a comprehensive narrative review. Pharmaceuticals. 2026;19(3):408. https://doi.org/10.3390/ph19030408.

7. Yanai H, Adachi H, Hakoshima M, Iida S, Katsuyama H. Metabolicdysfunction-associated steatotic liver disease – its pathophysiology, association with atherosclerosis and cardiovascular disease, and treatments. Int J Mol Sci. 2023;24(20):15473. https://doi.org/10.3390/ijms242015473.

8. Younossi ZM, Golabi P, Paik JM, Henry A, Van Dongen C, Henry L. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review. Hepatology. 2023;77(4):1335–1347. https://doi.org/10.1097/HEP.0000000000000004.

9. Martinez-Dominguez SJ, Garcia-Mateo S, Gargallo-Puyuelo CJ, Gallego-Llera B, Callau P, Mendi C et al. Inflammatory bowel disease is an independent risk factor for metabolic dysfunction-associated steatotic liver disease in lean individuals. Inflamm Bowel Dis. 2024;30(8):1274–1283. https://doi.org/10.1093/ibd/izad175.

10. Chuang MH, Chen JY, Wang HY, Jiang ZH, Wu VC. Clinical outcomes of tirzepatide or GLP-1 receptor agonists in individuals with type 2 diabetes. JAMA Netw Open. 2024;7(8):e2427258. https://doi.org/10.1001/jamanetworkopen.2024.27258.

11. Younossi ZM, Golabi P, Paik J, Owrangi S, Yilmaz Y, El-Kassas M et al. Prevalence of metabolic dysfunction-associated steatotic liver disease in the Middle East and North Africa. Liver Int. 2024;44(5):1061–1070. https://doi.org/10.1111/liv.15852.

12. Konyn P, Ahmed A, Kim D. Causes and risk profiles of mortality among individuals with nonalcoholic fatty liver disease. Clin Mol Hepatol. 2023;29(Suppl.):S43–S57. https://doi.org/10.3350/cmh.2022.0351.

13. Targher G, Valenti L, Byrne CD. Metabolic dysfunction-associated steatotic liver disease. N Engl J Med. 2025;393(7):683–698. https://doi.org/10.1056/NEJMra2412865.

14. Younossi ZM, Kalligeros M, Henry L. Epidemiology of metabolic dysfunctionassociated steatotic liver disease. Clin Mol Hepatol. 2025;31(Suppl.):S32–S50. https://doi.org/10.3350/cmh.2024.0431.

15. Eslam M, Newsome PN, Sarin SK, Anstee QM, Targher G, Romero-Gomez M et al. A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement. J Hepatol. 2020;73(1):202–209. https://doi.org/10.1016/j.jhep.2020.03.039.

16. Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, Abdelmalek MF, Caldwell S, Barb D et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77(5):1797–1835. https://doi.org/10.1097/HEP.0000000000000323.

17. Miao L, Targher G, Byrne CD, Cao YY, Zheng MH. Current status and future trends of the global burden of MASLD. Trends Endocrinol Metab. 2024;35(8):697–707. https://doi.org/10.1016/j.tem.2024.02.007.

18. Targher G, Byrne CD, Tilg H. MASLD: a systemic metabolic disorder with cardiovascular and malignant complications. Gut. 2024;73(4):691–702. https://doi.org/10.1136/gutjnl-2023-330595.

19. Peverelle M, Mbelle M, Joshi D. New names, new drugs, better outcomes in steatotic liver disease. Br J Hosp Med. 2025;86(8):1–18. https://doi.org/10.12968/hmed.2024.0655.

20. Stefan AG, Mitrea A, Clenciu D, Vladu IM, Roşu MM, Protasiewicz-Timofticiuc DC et al. MASH in type 2 diabetes: pathophysiology, diagnosis, and therapeutic management – a narrative review. Medicina. 2026;62(2):325. https://doi.org/10.3390/medicina62020325.

21. Лазебник ЛБ. Метаболически ассоциированная жировая болезнь печени. Практические рекомендации Научного общества гастроэнтерологов России. Часть 1. Экспериментальная и клиническая гастроэнтерология. 2024;(10):5–10. https://doi.org/10.31146/1682-8658-ecg-230-10-5-10.

22. Acierno C, Caturano A, Pafundi PC, Nevola R, Adinolfi LE, Sasso FC. Nonalcoholic fatty liver disease and type 2 diabetes: pathophysiological mechanisms shared between the two faces of the same coin. Explor Med. 2020;1:287–306. https://doi.org/10.37349/emed.2020.00019.

23. Devasia AG, Ramasamy A, Leo CH. Current therapeutic landscape for metabolic dysfunction-associated steatohepatitis. Int J Mol Sci. 2025;26(4):1778. https://doi.org/10.3390/ijms26041778.

24. Patel AH, Peddu D, Amin S, Elsaid MI, Minacapelli CD, Chandler TM et al. Nonalcoholic fatty liver disease in lean/nonobese and obese individuals: a comprehensive review on prevalence, pathogenesis, clinical outcomes, and treatment. J Clin Transl Hepatol. 2023;11(2):502–515. https://doi.org/10.14218/JCTH.2022.00204.

25. Cotter TG, Rinella M. Nonalcoholic fatty liver disease 2020: the state of the disease. Gastroenterology. 2020;158(7):1851–1864. https://doi.org/10.1053/j.gastro.2020.01.052.

26. Tanase DM, Gosav EM, Costea CF, Ciocoiu M, Lacatusu CM, Maranduca MA et al. The intricate relationship between type 2 diabetes mellitus (T2DM), insulin resistance (IR), and nonalcoholic fatty liver disease (NAFLD). J Diabetes Res. 2020;2020:3920196. https://doi.org/10.1155/2020/3920196.

27. Hashim MMA, Khan M, Ashraf M, Mohsin S, Zahoor K, Niazi J et al. Pathological evolution and internal medicine management of nonalcoholic fatty liver disease (NAFLD) in the era of metabolic dysfunctionassociated steatotic liver disease (MASLD). Cureus. 2025;17(6):e86963. https://doi.org/10.7759/cureus.86963.

28. Moncho F, Benlloch S, Górriz JL. The impact of metabolic dysfunctionassociated steatotic liver disease (MASH) on the high risk of cardiovascular disease in CKD: interconnections and management. Clin Kidney J. 2025;18(9):260. https:/doi.org/10.1093/ckj/sfaf260.

29. Hernandez-Ceballos W, Cordova-Gallardo J, Mendez-Sanchez N. Gut microbiota in metabolic-associated fatty liver disease and in other chronic metabolic diseases. J Clin Transl Hepatol. 2021;9(2):227–238. https://doi.org/10.14218/JCTH.2020.00131.

30. Hao X, Song H, Su X, Li J, Ye Y, Wang C et al. Prophylactic effects of nutrition, dietary strategies, exercise, lifestyle and environment on nonalcoholic fatty liver disease. Ann Med. 2025;57(1):2464223. https://doi.org/10.1080/07853890.2025.2464223.

31. Devarbhavi H, Asrani SK, Arab JP, Nartey YA, Pose E, Kamath PS. Global burden of liver disease: 2023 update. J Hepatol. 2023;79(2):516–537. https://doi.org/10.1016/j.jhep.2023.03.017.

32. Handelsman Y, Anderson JE, Bakris GL, Ballantyne CM, Bhatt DL, Bloomgarden ZT et al. DCRM 2.0: multispecialty practice recommendations for the management of diabetes, cardiorenal, and metabolic diseases. Metabolism. 2024;159:155931. https://doi.org/10.1016/j.metabol.2024.155931.

33. Long MT, Noureddin M, Lim JK. AGA Clinical Practice Update: diagnosis and management of nonalcoholic fatty liver disease in lean individuals: expert review. Gastroenterology. 2022;163(3):764–774. https://doi.org/10.1053/j.gastro.2022.06.023.

34. Djeagou A, Gunukula K, Sermani A, Vaspari SK. Emerging perspectives in the diagnosis and management of metabolic dysfunction-associated steatotic liver disease (MASLD): a narrative review. Cureus. 2025;17(10):e95288. https://doi.org/10.7759/cureus.95288.

35. Mahady SE, George J. Predicting the future burden of NAFLD and NASH. J Hepatol. 2018;69(4):774–775. https://doi.org/10.1016/j.jhep.2018.06.025.

36. Zafer M, Tavaglione F, Romero-Gomez M, Loomba R. Review article: GLP-1 receptor agonists and glucagon/GIP/GLP-1 receptor dual or triple agonists – mechanism of action and emerging therapeutic landscape in MASLD. Aliment Pharmacol Ther. 2025;61(12):1872–1888. https://doi.org/10.1111/apt.70196.

37. 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):205–216. https://doi.org/10.1056/NEJMoa2206038.

38. Mega A, Turri C, Marzi L, Dauriz M, Sacco R, Floreani A, Stasi C. New treatment options for MASLD patients with type 2 diabetes. Life. 2026;16(2):254. https://doi.org/10.3390/life16020254.

39. da Silva Lima N, Cabaleiro A, Novoa E, Riobello C, Knerr PJ, He Y et al. GLP-1 and GIP agonism has no direct actions in human hepatocytes or hepatic stellate cells. Cell Mol Life Sci. 2024;81(1):468. https://doi.org/10.1007/s00018-024-05507-6.

40. Targher G, Mantovani A, Byrne CD. Mechanisms and possible hepatoprotective effects of glucagon-like peptide-1 receptor agonists and other incretin receptor agonists in non-alcoholic fatty liver disease. Lancet Gastroenterol Hepatol. 2023;8(2):179–191. https://doi.org/10.1016/S24681253(22)00338-7.

41. Kosiborod MN, Abildstrom SZ, Borlaug BA, Butler J, Rasmussen S, Davies M et al. Semaglutide in patients with heart failure with preserved ejection fraction and obesity. N Engl J Med. 2023;389(12):1069–1084. https://doi.org/10.1056/NEJMoa2306963.

42. Borges RDS, Abreu ES, Berton GG, de Paula LH, Conegundes AF, Martins JMB et al. Efficacy and safety of GLP-1 receptor agonists in MASH with fibrosis: a systematic review and meta-analysis. JHEP Rep. 2026;8:101708. https://doi.org/10.1016/j.jhepr.2025.101708.

43. Mantovani A, Morandin R, Fiorio V, Lando MG, Stefan N, Tilg H et al. Glucagon-like peptide-1 receptor agonists improve MASH and liver fibrosis: a meta-analysis of randomised controlled trials. Liver Int. 2025;45(9):e70256. https://doi.org/10.1111/liv.70256.

44. Alkhatib M, Almasri N, Alshwayyat S, Almahariq H, Hammadeh BM, Taimeh Z et al. The multifaceted effects of semaglutide: exploring its broad therapeutic applications. Future Sci OA. 2025;11(1):2483607. https://doi.org/10.1080/20565623.2025.2483607.

45. Alharbi AG. GLP-1 receptor agonism: a transformative approach for managing type-2 diabetes and obesity. Saudi Pharm J. 2025;33(5):34. https://doi.org/10.1007/s44446-025-00038-y.

46. Zacharia GS, Ashraf MH, Sosa F, Jacob A, Patel H. Quick glance at ‘metabolic dysfunction associated steatotic liver disease’ therapeutics: targets, trials, and trends. World J Gastrointest Pharmacol Ther. 2025;16(4):110827. https://doi.org/10.4292/wjgpt.v16.i4.110827.

47. Ghaleb J, Khouzami KK, Nassif N, Attieh P, Ajlani MFA, Sleiman JB et al. Unveiling tirzepatide’s therapeutic spectrum: a dual GIP/GLP-1 agonist targeting metabolic, neurological, and cardiovascular health. Int J Endocrinol. 2025;2025:2876156. https://doi.org/10.1155/ije/2876156.

48. Banji D, Alshahrani S, Alfarhan M, Banji OJF. Revolutionizing type 2 diabetes management: the role of the pharmacist in unlocking the potential of tirzepatide. Saudi Pharm J. 2025;33(6):51. https://doi.org/10.1007/s44446-025-00050-2.

49. Kahl S, Gancheva S, Strassburger K, Herder C, Machann J, Katsuyama H et al. Empagliflozin effectively lowers liver fat content in wellcontrolled type 2 diabetes: a randomized, double-blind, phase 4, placebo-controlled trial. Diabetes Care. 2020;43(2):298–305. https://doi.org/10.2337/dc19-0641.

50. Loomba R, Hartman ML, Lawitz EJ, Vuppalanchi R, Boursier J, Bugianesi E et al. Tirzepatide for metabolic dysfunction-associated steatohepatitis with liver fibrosis. N Engl J Med. 2024;391(4):299–310. https://doi.org/10.1056/NEJMoa2401943.

51. Newsome PN, Loomba R. Therapeutic horizons in metabolic dysfunctionassociated steatohepatitis. J Clin Invest. 2025;135(13):e186425. https://doi.org/10.1172/JCI186425.

52. Drygalski K. Pharmacological treatment of MASLD: contemporary treatment and future perspectives. Int J Mol Sci. 2025;26(13):6518. https://doi.org/10.3390/ijms26136518.

53. Hartman ML, Sanyal AJ, Loomba R, Wilson JM. Nikooienejad A, Bray R et al. Effects of Novel Dual GIP and GLP-1 Receptor Agonist Tirzepatide on Biomarkers of Nonalcoholic Steatohepatitis in Patients With Type 2 Diabetes. Diabetes Care. 2020;43(6):1352–1355. https://doi.org/10.2337/dc19-1892.

54. Sanyal AJ, Kaplan LM, Frias JP, Brouwers B, Wu Q, Thomas MK et al. Triple hormone receptor agonist retatrutide for metabolic dysfunctionassociated steatotic liver disease: a randomized phase 2a trial. Nat Med. 2024;30(7):2037–2048. https://doi.org/10.1038/s41591-024-03018-2.

55. Ullah MI, Tamanna S. Obesity: clinical impact, pathophysiology, complications, and modern innovations in therapeutic strategies. Medicines. 2025;12(3):19. https://doi.org/10.3390/medicines12030019.

56. Луговик ИА, Бабина АВ, Арутюнян СС, Ермолаева ДО, Сапарова ВБ, Кобелева ТН и соавт. Первый дженерик тирзепатида GP30931: физико-химическое и биологическое сходство с референтным лекарственным средством. Разработка и регистрация лекарственных средств. 2025;14(2):54–74. https://doi.org/10.33380/2305-2066-2025-14-2-2084.

57. Демидова ТЮ, Кисляк ОА, Стародубова АВ, Никитин ИГ, Ушанова ФО. За пределами ИМТ: обсуждаем новую концепцию определения и диагностики клинического ожирения. Медицинский совет. 2025;19(6):240–252. https://doi.org/10.21518/ms2025-183.

58. Демидова ТЮ, Измайлова МЯ. Новые горизонты в управлении метаболическими заболеваниями: фокус на эффективность и безопасность тирзепатида. FOCUS Эндокринология. 2025;6(3):12–23. https://doi.org/10.62751/2713-0177-2025-6-3-03.

59. Xiao Z, Li X, Gong J, Zhou F. Comparative efficacy of multiple drugs for nonalcoholic fatty liver disease: a Bayesian network meta-analysis. Eur J Med Res. 2025;30(1):1164. https://doi.org/10.1186/s40001-025-03445-y.

60. Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB 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. https://doi.org/10.1016/j.molmet.2018.09.009.