Новые горизонты лечения сахарного диабета 2-го типа и управление прогнозом с помощью агонистов рецепторов глюкагоноподобного пептида-1

Сахарный диабет 2-го типа (СД2) – хроническое заболевание, которое набирает масштаб эпидемии по всему миру. Основными факторами роста распространенности СД2 являются урбанизация, старение населения и снижение физической активности, что приводит к увеличению случаев ожирения. В настоящее время ожирение и СД2 остаются ключевыми причинами развития коморбидной патологии и способствуют росту смертности в глобальном масштабе. В статье рассматривается роль жировой ткани и инсулинорезистентности в патогенезе СД2. Уделено внимание значению энтероинсулярной оси, а также гормонам-инкретинам, которые занимают важное место в регуляции углеводного обмена. Среди них наиболее изучен глюкагоноподобный пептид-1 (ГПП-1) – гормон, обладающий как панкреатическим, так и внепанкреатическим действием. Благодаря более глубокому пониманию механизмов развития заболеваний стало возможным расширение спектра сахароснижающих препаратов. Многогранный патогенез СД2 требует комплексного воздействия, направленного на различные звенья развития болезни. Такой мультитаргетный подход позволяет достичь более выраженного и устойчивого сахароснижающего эффекта, сохранить гликемический контроль на разных этапах прогрессирования болезни. При этом акцент делается на важности персонализированного выбора лекарственной терапии. Актуальные рекомендации предлагают рассматривать агонисты рецепторов ГПП-1 (арГПП-1) как вариант препаратов первой линии в стартовой терапии СД2, включая возможность их комбинированного использования с другими сахароснижающими препаратами (ССП). Общепризнана эффективность арГПП-1 в улучшении исходов сердечно-сосудистых заболеваний (ССЗ). В статье представлены данные клинических исследований семаглутида, которые оценивают его эффективность, безопасность и переносимость. Обсуждаются фармакологические особенности, терапевтические преимущества препарата на основании результатов сравнительных исследований с другими представителями группы арГПП-1, а также другими группами ССП. Помимо обсуждения основного действия семаглутида, направленного на улучшение гликемического контроля и снижение массы тела, уделено внимание дополнительным положительным эффектам, таким как снижение артериального давления и улучшение параметров липидного обмена.

1. Lovic D, Piperidou A, Zografou I, Grassos H, Pittaras A, Manolis A. The Growing Epidemic of Diabetes Mellitus. Curr Vasc Pharmacol. 2020;18(2):104–109. https://doi.org/10.2174/1570161117666190405165911.

2. Guzman-Vilca WC, Carrillo-Larco RM. Number of People with Type 2 Diabetes Mellitus in 2035 and 2050: A Modelling Study in 188 Countries. Curr Diabetes Rev. 2024;21(1):e120124225603. https://doi.org/10.2174/0115733998274323231230131843.

3. Klein S, Gastaldelli A, Yki-Järvinen H, Scherer PE. Why does obesity cause diabetes? Cell Metab. 2022;34(1):11–20. https://doi.org/10.1016/j.cmet.2021.12.012.

4. Blüher M. Obesity: Global epidemiology and pathogenesis. Nat Rev Endocrinol. 2019;15:288–298. https://doi.org/10.1038/s41574-019-0176-8.

5. Malik VS, Willet WC, Hu FB. Nearly a decade on – trends, risk factors and policy implications in global obesity. Nat Rev Endocrinol. 2020;16:615–616. https://doi.org/10.1038/s41574-020-00411-y.

6. Jin X, Qiu T, Li L, Yu R, Chen X, Li C et al. Pathophysiology of obesity and its associated diseases. Acta Pharmaceutica Sinica. 2023;13(6):2403–2424. https://doi.org/10.1016/j.apsb.2023.01.012.

7. Zhao , Zhang P., Lee JT, Oldenburg B, van Heusden A, Haregu TN et al. The Prevalence of Metabolic Disease Multimorbidity and Its Associations with Spending and Health Outcomes in Middle-Aged and Elderly Chinese Adults. Front Public Health. 2021;9:658706. https://doi.org/10.3389/fpubh.2021.658706.

8. Dedov I, Shestakova M, Benedetti MM, Simon D, Pakhomov I, Galstyan G. Prevalence of Type 2 diabetes mellitus (T2DM) in the adult Russian population (NATION study). Diab Res Clin Prac. 2016;115:90–95. https://doi.org/10.1016/j.diabres.2016.02.010.

9. Дедов ИИ, Шестакова МВ, Сухарева ОЮ, Мокрышева НГ, Андреева ЕН, Безлепкина ОБ и др. Алгоритмы специализированной медицинской помощи больным сахарным диабетом / Под редакцией И.И. Дедова, М.В. Шестаковой, О.Ю. Сухаревой. 12-й выпуск. Сахарный диабет. 2025;28(5S):1–175. https://doi.org/10.14341/DM20255S.

10. Чумакова ГА, Кузнецова ТЮ, Дружилов МА, Гриценко ОВ. Метаболическое здоровье населения: современный взгляд на проблему и пути ее решения. Российский кардиологический журнал. 2024;29(5):5896. https://doi.org/10.15829/1560-4071-2024-5896.

11. van Vliet S, Koh HE, Patterson BW, Yoshino M, LaForest R, Gropler RJ et al. Obesity Is Associated With Increased Basal and Postprandial β-Cell Insulin Secretion Even in the Absence of Insulin Resistance. Diabetes. 2020;69(10):2112–2119. https://doi.org/10.2337/db20-0377.

12. Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. Beta-cell deficit and increased beta-cell apoptosis in humans with Type 2 diabetes. Diabetes. 2003;52(1):102–110. https://doi.org/10.2337/diabetes.52.1.102.

13. Saisho Y, Butler AE, Manesso E, Elashoff D, Rizza RA, Butler PC. β-cell mass and turnover in humans: effects of obesity and aging. Diabetes Care. 2013;36(1):111–117. https://doi.org/10.2337/dc12-0421.

14. Linnemann AK, Baan M, Davis DB. Pancreatic β-cell proliferation in obesity. Adv Nutr. 2014;5(3):278–288. https://doi.org/10.3945/an.113.005488.

15. Poitout V, Amyot J, Semache M, Zarrouki B, Hagman D, Fontés G. Glucolipotoxicity of the pancreatic beta cell. Biochim Biophys Acta. 2010;1801(3):289–298. https://doi.org/10.1016/j.bbalip.2009.08.006.

16. Prentki M, Peyot ML, Masiello P, Madiraju SRM. Nutrient-Induced Metabolic Stress, Adaptation, Detoxification, and Toxicity in the Pancreatic β-Cell. Diabetes. 2020;69(3):279–290. https://doi.org/10.2337/dbi19-0014.

17. Hossan T, Kundu S, Alam SS, Nagarajan S. Epigenetic Modifications Associated with the Pathogenesis of Type 2 Diabetes Mellitus. Endocr Metab Immune Disord Drug Targets. 2019;19(6):775–786. https://doi.org/10.2174/1871530319666190301145545.

18. Yaribeygi H, Maleki M, Sathyapalan T, Jamialahmadi T, Sahebkar A. Pathophysiology of Physical Inactivity-Dependent Insulin Resistance: A Theoretical Mechanistic Review Emphasizing Clinical Evidence.J Diabetes Res. 2021;2021:7796727. https://doi.org/10.1155/2021/7796727.

19. Iaccarino G, Franco D, Sorriento D, Strisciuglio T, Barbato E, Morisco C. Modulation of insulin sensitivity by exercise training: implications for cardiovascular prevention. J Cardio Transl Res. 2021;14(2):256–270. https://doi.org/10.1007/s12265-020-10057-w.

20. Coppack SW. Pro-inflammatory cytokines and adipose tissue. Proc Nutr Soc. 2001;60(3):349–356. https://doi.org/10.1079/pns2001110.

21. Романцова ТИ. Жировая ткань: цвета, депо и функции. Ожирение и метаболизм. 2021;18(3):282–301. https://doi.org/10.14341/omet12748.

22. Nakamura K, Fuster JJ, Walsh K. Adipokines: A link between obesity and cardiovascular disease. J Cardiol. 2014;63(4):250–259. https://doi.org/10.1016/j.jjcc.2013.11.006.

23. Fasshauer M, Blüher M. Adipokines in health and disease. Trends Pharmacol Sci. 2015;36(7):461–470. https://doi.org/10.1016/j.tips.2015.04.014.

24. Wondmkun YT. Obesity, Insulin Resistance, and Type 2 Diabetes: Associations and Therapeutic Implications. Diabetes Metab Syndr Obes. 2020;13:3611–3616. https://doi.org/10.2147/DMSO.S275898.

25. Michailidou Z, Gomez-Salazar M, Alexaki VI. Innate Immune Cells in the Adipose Tissue in Health and Metabolic Disease. J Innate Immun. 2022;14(1):4–30. https://doi.org/10.1159/000515117.

26. DeMarsilis A, Reddy N, Boutari C, Filippaios A, Sternthal E, Katsiki N et al. Pharmacotherapy of Type 2 diabetes: An update and future directions. Metabolism. 2022;137:155332. https://doi.org/10.1016/j.metabol.2022.155332.

27. Lu X, Xie Q, Pan X, Zhang R, Zhang X, Peng G et al. Type 2 diabetes mellitus in adults: pathogenesis, prevention and therapy. Signal Transduct Target Ther. 2024;9(1):262. https://doi.org/10.1038/s41392-024-01951-9.

28. American Diabetes Association. 9. Pharmacologic approaches to glycemic treatment: standards of care in diabetes – 2025. Diabetes Care. 2025;48(Suppl. 1):S181–S206. https://doi.org/10.2337/dc25-S009.

29. Gourdy P, Darmon P, Dievart F, Halimi JM, Guerci B. Combining glucagonlike peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) in patients with Type 2 diabetes mellitus (T2DM) Cardiovasc. Diabetol. 2023;22:79. https://doi.org/10.1186/s12933-023-01798-4.

30. Müller TD, Finan B, Bloom SR, D’Alessio D, Drucker DJ, Flatt PR et al. Glucagon-like peptide 1 (GLP-1). Mol Metab. 2019;30:72–130. https://doi.org/10.1016/j.molmet.2019.09.010.

31. American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2021. Diabetes Care. 2021;44(Suppl. 1):S15–S33. https://doi.org/10.2337/dc21-S002.

32. Usama RY. Sitagliptin/MET The Drug of Choice: Case Scenarios. Diabetes Metab Syndr. Available at: https://www.slideshare.net/slideshow/sitagliptin-met-the-drug-of-choice-case-scenarios/278272676.

33. Hamed K, Alosaimi MN, Ali BA, Alghamdi A, Alkhashi T, Alkhaldi SS et al. Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists: Exploring Their Impact on Diabetes, Obesity, and Cardiovascular Health Through a Comprehensive Literature Review. Cureus. 2024;16(9):e68390. https://doi.org/10.7759/cureus.68390.

34. Nauck MA, Homberger E, Siegel EG, Allen RC, Eaton RP, Ebert R et al. Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses. J Clin Endocrinol Metab. 1986;63(2):492–498. https://doi.org/10.1210/jcem-63-2-492.

35. Madsbad S. The role of glucagon-like peptide-1 impairment in obesity and potential therapeutic implications. Diabetes Obes Metab. 2014;16(1):9–21. https://doi.org/10.1111/dom.12119.

36. Orskov C, Wettergren A, Holst JJ. Secretion of the incretin hormones glucagon-like peptide-1 and gastric inhibitory polypeptide correlates with insulin secretion in normal man throughout the day. Scand J Gastroenterol. 1996;31(7):665–670. https://doi.org/10.3109/00365529609009147.

37. Lim GE, Brubaker PL. Glucagon-like peptide 1 secretion by the L-cell – the view from within. Diabetes. 2006;55:S70–S77. https://doi.org/10.2337/db06-S020.

38. Eissele R, Göke R, Willemer S, Harthus HP, Vermeer H, Arnold R et al. Glucagon-like peptide-1 cells in the gastrointestinal tract and pancreas of rat, pig and man. Eur J Clin Invest. 1992;22(4):283–291. https://doi.org/10.1111/j.1365-2362.1992.tb01464.x.

39. Meier JJ, Nauck MA, Kranz D, Holst JJ, Deacon CF, Gaeckler D et al. Secretion, degradation, and elimination of glucagon-like peptide 1 and gastric inhibitory polypeptide in patients with chronic renal insufficiency and healthy control subjects. Diabetes. 2004;53(3):654–662. https://doi.org/10.2337/diabetes.53.3.654.

40. Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007;87(4):1409–1439. https://doi.org/10.1152/physrev.00034.2006.

41. Kjems LL, Holst JJ, Vølund A, Madsbad S. The influence of GLP-1 on glucose-stimulated insulin secretion: effects on beta-cell sensitivity in Type 2 and nondiabetic subjects. Diabetes. 2003;52(2):380–386. https://doi.org/10.2337/diabetes.52.2.380.

42. Ahmad K, Shaikh S, Lim JH, Ahmad SS, Chun HJ, Lee EJ et al. Therapeutic application of natural compounds for skeletal muscle-associated metabolic disorders: A review on diabetes perspective. Biomed Pharmacother. 2023;168:115642. https://doi.org/10.1016/j.biopha.2023.115642.

43. Rizzo M, Nauck MA, Mantzoros CS. Incretin-based therapies in 2021 – Current status and perspectives for the future. Metabolism. 2021;122:154843. https://doi.org/10.1016/j.metabol.2021.154843.

44. Тюренков ИН, Бакулин ДА, Куркин ДВ, Волотова ЕВ. Кардиоваскулярные эффекты инкретиномиметиков и их терапевтический потенциал. Вестник Российской академии медицинских наук. 2017;72(1):66–75. Режим доступа: https://vestnikramn.spr-journal.ru/jour/article/view/732.

45. Hernández C, Bogdanov P, Corraliza L, García-Ramírez M, Solà-Adell C, Arranz JA et al. Topical Administration of GLP-1 Receptor Agonists Prevents Retinal Neurodegeneration in Experimental Diabetes. Diabetes. 2016;65(1):172–187. https://doi.org/10.2337/db15-0443.

46. Drucker DJ. GLP-1 physiology informs the pharmacotherapy of obesity. Mol Metab. 2022;57:101351. https://doi.org/10.1016/j.molmet.2021.101351.

47. Williams DL. The diverse effects of brain glucagon-like peptide 1 receptors on ingestive behaviour. Br J Pharmacol. 2022;179(4):571–583. https://doi.org/10.1111/bph.15535.

48. Brierley DI, de Lartigue G. Reappraising the role of the vagus nerve in GLP-1-mediated regulation of eating. Br J Pharmacol. 2022;179(4):584–599. https://doi.org/10.1111/bph.15603.

49. Nauck MA, Petrie JR, Sesti G, Mannucci E, Courrèges JP, Lindegaard ML et al. 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):231–241. https://doi.org/10.2337/dc15-0165.

50. Davies M, Pieber TR, Hartoft-Nielsen ML, Hansen OKH, Jabbour S, Rosenstock J. Effect of Oral Semaglutide Compared With Placebo and Subcutaneous Semaglutide on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Clinical Trial AMA. 2017;318(15):1460–1470. https://doi.org/10.1001/jama.2017.14752.

51. Tamayo-Trujillo R, Ruiz-Pozo VA, Cadena-Ullauri S, Guevara-Ramírez P, Paz-Cruz E, Zambrano-Villacres R et al. Molecular mechanisms of semaglutide and liraglutide as a therapeutic option for obesity. Front Nutr. 2024;11:1398059. https://doi.org/10.3389/fnut.2024.1398059.

52. Drucker DJ. The benefits of GLP-1 drugs beyond obesity. Science. 2024;385(6706):258–260. https://doi.org/10.1126/science.adn4128.

53. Ten Kulve JS, Veltman DJ, van Bloemendaal L, Barkhof F, Drent ML, Diamant M et al. Liraglutide Reduces CNS Activation in Response to Visual Food Cues Only After Short-term Treatment in Patients With Type 2 Diabetes. Diabetes Care. 2016;39(2):214–221. https://doi.org/10.2337/dc15-0772.

54. Masaki T, Ozeki Y, Yoshida Y, Okamoto M, Miyamoto S, Gotoh K et al. Glucagon-Like Peptide-1 Receptor Agonist Semaglutide Improves Eating Behavior and Glycemic Control in Japanese Obese Type 2 Diabetic Patients. Metabolites. 2022;12(2):147. https://doi.org/10.3390/metabo12020147.

55. Cheney C, Hunter K, Klein M. Impact of GLP-1 Receptor Agonists on Perceived Eating Behaviors in Response to Stimuli. Diabetes Metab Syndr Obes. 2025;18:1411–1418. https://doi.org/10.2147/DMSO.S488806.

56. Drucker DJ. Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity. Diabetes Care. 2024;47(11):1873–1888. https://doi.org/10.2337/dci24-0003.

57. Cornell S. A review of GLP-1 receptor agonists in Type 2 diabetes: A focus on the mechanism of action of once-weekly agents. J Clin Pharm Ther. 2020;45(Suppl. 1):17–27. https://doi.org/10.1111/jcpt.13230.

58. Michos ED, Lopez-Jimenez F, Gulati M. Role of Glucagon-Like Peptide-1 Receptor Agonists in Achieving Weight Loss and Improving Cardiovascular Outcomes in People With Overweight and Obesity. J Am Heart Assoc. 2023;12(11):e029282. https://doi.org/10.1161/JAHA.122.029282.

59. Salvador R, Moutinho CG, Sousa C, Vinha AF, Carvalho M, Matos C. Semaglutide as a GLP-1 Agonist: A Breakthrough in Obesity Treatment. Pharmaceuticals. 2025;18(3):399. https://doi.org/10.3390/ph18030399.

60. Lau J, Bloch P, Schäffer L, Pettersson I, Spetzler J, Kofoed J et al. Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide. J Med Chem. 2015;58(18):7370–7380. https://doi.org/10.1021/acs.jmedchem.5b00726.

61. Aroda VR, Ahmann A, Cariou B, Chow F, Davies MJ, Jódar E et al. Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of Type 2 diabetes: Insights from the SUSTAIN 1-7 trials. Diabetes Metab. 2019;45(5):409–418. https://doi.org/10.1016/j.diabet.2018.12.001.

62. DeSouza C, Cariou B, Garg S, Lausvig N, Navarria A, Fonseca V. Efficacy and Safety of Semaglutide for Type 2 Diabetes by Race and Ethnicity: A Post Hoc Analysis of the SUSTAIN Trials. J Clin Endocrinol Metab. 2020;105(2):dgz072. https://doi.org/10.1210/clinem/dgz072.

63. Cornier MA. A review of current guidelines for the treatment of obesity. Am J Manag Care. 2022;28(15 Suppl.):S288–S296. https://doi.org/10.37765/ajmc.2022.89292.

64. Russell-Jones D, Khan R. Insulin-associated weight gain in diabetes – causes, effects and coping strategies. Diabetes Obes Metab. 2007;9(6):799–812. https://doi.org/10.1111/j.1463-1326.2006.00686.x.

65. Ahrén B, Atkin SL, Charpentier G, Warren ML, Wilding JPH, Birch S et al. Semaglutide induces weight loss in subjects with Type 2 diabetes regardless of baseline BMI or gastrointestinal adverse events in the SUSTAIN 1 to 5 trials. Diabetes Obes Metab. 2018;20(9):2210–2219. https://doi.org/10.1111/dom.13353.

66. Shi FH, Li H, Cui M, Zhang ZL, Gu ZC, Liu XY. Efficacy and Safety of Once-Weekly Semaglutide for the Treatment of Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Front Pharmacol. 2018;9:576. https://doi.org/10.3389/fphar.2018.00576.

67. Davies M, Færch L, Jeppesen OK, Pakseresht A, Pedersen SD, Perreault L et al. 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):971–984. https://doi.org/10.1016/S0140-6736(21)00213-0.

68. Lingvay I, Hansen T, Macura S, Marre M, Nauck MA, de la Rosa R et al. Superior weight loss with once-weekly semaglutide versus other glucagonlike peptide-1 receptor agonists is independent of gastrointestinal adverse events. BMJ Open Diabetes Res Care. 2020;8(2):e001706. https://doi.org/10.1136/bmjdrc-2020-001706.

69. Capehorn MS, Catarig AM, Furberg JK, Janez A, Price HC, Tadayon S et al. Efficacy and safety of once-weekly semaglutide 1.0mg vs once-daily liraglutide 1.2mg as add-on to 1-3 oral antidiabetic drugs in subjects with Type 2 diabetes (SUSTAIN 10). Diabetes Metab. 2020;46(2):100–109. https://doi.org/10.1016/j.diabet.2019.101117.

70. Pratley RE, Aroda VR, Lingvay I, Lüdemann J, Andreassen C, Navarria A et al. 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):275–286. https://doi.org/10.1016/S2213-8587(18)30024-X.

71. Alsugair HA, Alshugair IF, Alharbi TJ, Bin Rsheed AM., Tourkmani AM, AlMadani W. Weekly Semaglutide vs. Liraglutide Efficacy Profile: A Network Meta-Analysis. Healthcare. 2021;9(9):1125. https://doi.org/10.3390/healthcare9091125.

72. Xie Z, Yang S, Deng W, Li J, Chen J. Efficacy and Safety of Liraglutide and Semaglutide on Weight Loss in People with Obesity or Overweight: A Systematic Review. Clin Epidemiol. 2022;14:1463–1476. https://doi.org/10.2147/CLEP.S391819.

73. Разина АО, Руненко СД, Ачкасов ЕЕ. Проблема ожирения: современные тенденции в России и в мире. Вестник Российской академии медицин­ ских наук. 2016;71(2):154–159. https://doi.org/10.15690/vramn655.

74. Iacobellis G, Camarena V, Sant DW, Wang G. Human Epicardial Fat Expresses Glucagon-Like Peptide 1 and 2 Receptors Genes. Horm Metab Res. 2017;49(8):625–630. https://doi.org/10.1055/s-0043-109563.

75. Overgaard RV, Lindberg SØ, Thielke D. Impact on HbA1c and body weight of switching from other GLP-1 receptor agonists to semaglutide: A modelbased approach. Diabetes Obes Metab. 2019;21(1):43–51. https://doi.org/10.1111/dom.13479.

76. Abdul-Ghani MA, DeFronzo RA. Pathogenesis of insulin resistance in skeletal muscle. J Biomed Biotechnol. 2010;2010:476279. https://doi.org/10.1155/2010/476279.

77. Blundell J, Finlayson G, Axelsen M, Flint A, Gibbons C, Kvist T et al. 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;19:1242–1251. https://doi.org/10.1111/dom.12932.

78. Ozeki Y, Masaki T, Kamata A, Miyamoto S, Yoshida Y, Okamoto M et al. The Effectiveness of GLP-1 Receptor Agonist Semaglutide on Body Composition in Elderly Obese Diabetic Patients: A Pilot Study. Medicines. 2022;9:47. https://doi.org/10.3390/medicines9090047.

79. Volpe S, Lisco G, Racaniello D, Fanelli M, Colaianni V, Vozza A et al. Once-Weekly Semaglutide Induces an Early Improvement in Body Composition in Patients with Type 2 Diabetes: A 26-Week Prospective Real-Life Study. Nutrients. 2022;14:2414. https://doi.org/10.3390/nu14122414.

80. Dal Canto E, Ceriello A, Rydén L, Ferrini M, Hansen TB, Schnell O et al. Diabetes as a cardiovascular risk factor: An overview of global trends of macro and micro vascular complications. Eur J Prev Cardiol. 2019;26(2 Suppl.):25–32. https://doi.org/10.1177/2047487319878371.

81. Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016;375(19):1834–1844. https://doi.org/10.1056/NEJMoa1607141.

82. Guijun HE, Hanxiong LIU, Zhang Z. Effects of semaglutide on cardiovascular outcomes in patients with obesity with or without diabetes: a meta-analysis based on randomized controlled trials. J Clin Cardiol. 2025;41(3):213–218. https://doi.org/10.13201/j.issn.1001-1439.2025.03.009.

83. Huang M, Wei R, Wang Y, Su T, Li Q, Yang X et al. Protective effect of glucagon‐like peptide‐1 agents on reperfusion injury for acute myocardial infarction: A meta‐analysis of randomized controlled trials. Ann Med. 2017;49:552–561. https://doi.org/10.1080/07853890.2017.1306653.

84. Ussher John R, Drucker Daniel J. Glucagon-like peptide 1 receptor agonists: cardiovascular benefits and mechanisms of action. Nat Rev Cardiol. 2023;20(7):463–474. https://doi.org/10.1038/s41569-023-00849-3.

85. Manubolu VS, Lakshmanan S, Kinninger A, Ahmad K, Susarla S, Seok HJ. et al. Effect of Semaglutide on Epicardial Adipose Tissue in Type 2 Diabetes: Insights From the STOP (Semaglutide Treatment effect On coronary atherosclerosis Progression) Randomized Trial. J Am Coll Cardiol. 2024;84(9):865–867. https://doi.org/10.1016/j.jacc.2024.05.065.

86. Iacobellis G. Epicardial adipose tissue in contemporary cardiology. Nat Rev Cardiol. 2022;19(9):593–606. https://doi.org/10.1038/s41569-022-00679-9.

87. Di 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):1287–1294. https://doi.org/10.1007/s00592-022-01936-6.

88. Tommerdahl KL, Nadeau KJ, Bjornstad P. Mechanisms of Cardiorenal Protection of Glucagon-Like Peptide-1 Receptor Agonists. Adv Chronic Kidney Dis. 2021;28(4):337–346. https://doi.org/10.1053/j.ackd.2021.06.001.

89. Jarvis H, Craig D, Barker R, Spiers G, Stow D, Anstee QM et al. Metabolic risk factors and incident advanced liver disease in non-alcoholic fatty liver disease (NAFLD): A systematic review and meta-analysis of population-based observational studies. PLoS Med. 2020;17(4):e1003100. https://doi.org/10.1371/journal.pmed.1003100.

90. Andreasen CR, Andersen A, Vilsbøll T. The future of incretins in the treatment of obesity and non-alcoholic fatty liver disease. Diabetologia. 2023;66(10):1846–1858. https://doi.org/10.1007/s00125-023-05966-9.

91. Katsuyama H, Hakoshima M, Kaji E, Mino M, Kakazu E, Iida S et al. Effects of Once-Weekly Semaglutide on Cardiovascular Risk Factors and Metabolic Dysfunction-Associated Steatotic Liver Disease in Japanese Patients with Type 2 Diabetes: A Retrospective Longitudinal Study Based on Real-World Data. Biomedicines. 2024;12:1001. https://doi.org/10.3390/biomedicines12051001.

92. Hachuła M, Kosowski M, Basiak M, Okopień B. Does Therapy with Glucagonlike Peptide 1 Receptor Agonists Have an Effect on Biochemical Markers of Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD)? Pleiotropic Metabolic Effect of Novel Antidiabetic Drugs in Patients with Diabetes – Interventional Study. Pharmaceuticals. 2023;16:1190. https://doi.org/10.3390/ph16091190.

93. Gad AI, Ibrahim NF, Almadani N, Mahfouz R, Nofal HA, El-Rafey DS et al. Therapeutic Effects of Semaglutide on Nonalcoholic Fatty Liver Disease with Type 2 Diabetes Mellitus and Obesity: An Open-Label Controlled Trial. Diseases. 2024;12(8):186. https://doi.org/10.3390/diseases12080186.