Study of mechanisms and approaches to incretin-based therapy for obesity in children
Abstract
This study highlights data on the increasing role of incretins in interdisciplinary therapy for endocrinopathies, particularly glucagon-like peptide-1 (GLP-1), which affects carbohydrate metabolism, insulin secretion, and other metabolic processes. The mechanisms of secretion, biological activity, and degradation of these peptides are described, along with their role in regulating appetite, gastrointestinal motility, and carbohydrate metabolism. This information allows for a comprehensive understanding of the effects of synthetic GLP-1 analogs. We also explore modern approaches to treating obesity in children and adolescents, including the use of GLP-1 receptor agonists such as liraglutide. It presents the results of a clinical study confirming the effectiveness and safety of liraglutide in reducing body weight and improving metabolic indicators in children with obesity. It is shown that liraglutide not only promotes weight loss but also has cardioprotective effects, improving lipid profiles and reducing blood pressure. The efficacy of liraglutide in children aged 12–18 with obesity was amount to 43.3 - 76.5%. The prevalence of hypertension in obese children decreased from 30.9% to 4.8%, carbohydrate metabolism disorders from 41.1% to 19.4%, dyslipidemia from 20.6% to 9.7%. Liraglutide reduces the risk of major adverse cardiovascular events by 13–22% in patients with type 2 diabetes and high cardiovascular risk. This effect is attributed to moderate blood pressure reduction, improved lipid profiles, enhanced endothelial function, and anti-inflammatory and antioxidant actions. Additionally, the article discusses the prospects for using GLP-1 receptor agonists in cardiology, including their ability to reduce the risk of cardiovascular events in patients with type 2 diabetes and obesity.
About the Authors
T. V. Chubarov
Voronezh Children's Clinical Hospital; N. N. Burdenko Voronezh State Medical University
Russian Federation
Russian Federation
Timofey V. Chubarov, Dr. Sci. (Med.), Chief Physician of the Voronezh Children's Clinical Hospital, Head of the Endocrinological Center, Associate Professor of the Department of Propaedeutics of Childhood Diseases and Polyclinic Pediatrics, N. N. Burdenko Voronezh State Medical University
16, Health Lane, Voronezh, 394018
I. E. Esaulenko
N. N. Burdenko Voronezh State Medical University
Russian Federation
Russian Federation
Igor E. Esaulenko, Dr. Sci. (Med.), Associate Professor, Rector
10, Studentskaya str., Voronezh, 394036
V. A. Peterkova
Russian National Research Center of Endocrinology of the Russian Ministry of Health
Russian Federation
Russian Federation
Valentina A. Peterkova, Academician of the Russian Academy of Sciences, Professor, Doctor of Medical Sciences, Chief Pediatric Endocrinologist of the Russian Ministry of Health, Head of the Department of Pediatric Endocrinology-Diabetology, Russian National Research Center of Endocrinology of the Russian Ministry of Health
11, Dmitry Ulyanov str., Moscow, 117292
O. A. Zhdanova
N. N. Burdenko Voronezh State Medical University
Russian Federation
Russian Federation
Olga A. Zhdanova, Dr. Sci. (Med.), Associate Professor, Professor of the Department of Clinical Pharmacology
10, Studentskaya str., Voronezh, 394036
W. Du
Harbin Medical University
China
China
Weijie Du, Professor of Department of Pharmacology, Vice Director of the Key Laboratory of Cardiovascular Medicine Research of Ministry of Education
157 Baojian Rd, Nangang, Harbin, 150088, Heilongjiang
O. G. Sharshova
Voronezh Children's Clinical Hospital; N. N. Burdenko Voronezh State Medical University
Russian Federation
Russian Federation
Olga G. Sharshova, Deputy Chief Physician on the medical part, Head of the Endocrinology Department, Pediatric Endocrinologist at the Voronezh Children's Clinical Hospital, N. N. Burdenko Voronezh State Medical University
16, Health Lane, Voronezh, 394018
References
1. Цыганкова ОВ, Веретюк ВВ, Аметов АС. Инкретины сегодня: множественные эффекты и терапевтический потенциал. Сахарный диабет. / Tsygankova OV, Veretyuk VV, Ametov AS. Incretins today: multiple effects and therapeutic potential. Diabetes Mellitus. 2019;22(1):70-78. https://doi.org/10.14341/dm9841. (In Russ.).
2. Демидова ТЮ, Лобанова КГ, Ойноткинова ОШ. Кишечная микробиота как эндокринный орган. Ожирение и метаболизм. / Demidova TY, Lobanova KG, Oynotkinova OS. Gut microbiota is an endocrine organ. Obesity and Metabolism. 2020;17(3):299-306. https://doi.org/10.14341/omet12457. (In Russ.).
3. Gautier J, Fetita S, Sobngwi E, Salaün-Martin C. Biological actions of the incretins GIP and GLP-1 and therapeutic perspectives in patients with type 2 diabetes. Diabetes & Metabolism. 2005;31(3):233-242. https://doi.org/10.1016/s1262-3636(07)70190-8.
4. Drucker DJ. MiniReview: The Glucagon-Like Peptides. Endocrinology. 2001;142(2):521-527. https://doi.org/10.1210/endo.142.2.7983.
5. Zhang X, Young RL, Bound M, et al. Comparative effects of proximal and distal small intestinal glucose exposure on glycemia, incretin hormone secretion, and the incretin effect in health and type 2 diabetes. Diabetes Care. 2019;42(4):520-528. https://doi.org/10.2337/dc18-2156.
6. Ким ЕИ, Ершова ЕВ, Мазурина НВ, Комшилова КА. Постбариатрические гипогликемии: взгляд эндокринолога. Ожирение и метаболизм. / Kim EI, Ershova EV, Mazurina NV, Komshilova KA. A view at postbariatric hypoglycemia by endocrinologist. Obesity and Metabolism. 2022;18(4):471-483. https://doi.org/10.14341/omet12785. (In Russ.).
7. Nauck MA, Kemmeries G, Holst JJ, Meier JJ. Rapid tachyphylaxis of the glucagonlike peptide 1-induced deceleration of gastric emptying in humans. Diabetes. 2011;60(5):1561-1565. https://doi.org/10.2337/db10-0474.
8. Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007;87(4):14091439. https://doi.org/10.1152/physrev.00034.2006.
9. Петеркова ВА, Безлепкина ОБ, Болотова НВ, и соавт. Клинические рекомендации «Ожирение у детей». Проблемы эндокринологии. / Peterkova VA, Bezlepkina OB, Bolotova NV, et al. Clinical guidelines «Obesity in children». Problems of Endocrinology. 2021;67(5):67-83. https://doi.org/10.14341/probl12802. (In Russ.).
10. Johnson VR, Washington TB, Chhabria S, et al. Food as medicine for obesity treatment and management. Clin Ther. 2022;44(5):671–681. https://doi.org/ 10.1016/J.CLINTHERA.2022.05.001.
11. Nicolucci A, Maffeis C. The adolescent with obesity: what perspectives for treatment? Ital J Pediatr. 2022;48(1). https://doi.org/10.1186/S13052-022-01205-W.
12. Smith JD, Fu E, Kobayashi MA. Prevention and Management of Childhood Obesity and Its Psychological and Health Comorbidities. Annu Rev Clin Psychol. 2020 May 7;16:351-378. https://doi.org/10.1146/annurev-clinpsy-100219-060201.
13. Kim A, Nguyen J, Babaei M, Kim A, Geller DH, Vidmar AP. A Narrative review: Phentermine and topiramate for the Treatment of Pediatric Obesity. Adolescent Health Medicine and Therapeutics. 2023;Volume 14:125-140. https://doi.org/10.2147/ahmt.s383454.
14. Kelly AS, Auerbach P, Barrientos-Perez M, Gies I, Hale PM, Marcus C, Mastrandrea LD, Prabhu N, Arslanian S; NN8022-4180 Trial Investigators. A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity. N Engl J Med. 2020 May 28;382(22):2117-2128. https://doi.org/10.1056/NEJMoa1916038.
15. Витебская АВ, Попович АВ. Опыт применения лираглутида у подростков с простым ожирением и сопутствующими заболеваниями желудочно-кишечного тракта. Ожирение и метаболизм. / Vitebskaya AV, Popovich AV. Liraglutide in adolescents with simple obesity and gastrointestinal comorbidities: treatment experience. Obesity and metabolism. 2023;20(2):124-130. https://doi.org/10.14341/omet12922. (In Russ.).
16. Шаршова ОГ, Чубаров ТВ, Петеркова ВА, Жданова ОА, Артющенко АИ. Эффек тивность и безопасность применения лираглутида в терапии детского ожирения. Вестник Российской академии медицинских наук. / Sharshova OG, Chubarov TV, Peterkova VA, Zhdanova OA, Artyushchenko AI. Effectiveness and safety of liraglutide in the treatment of childhood obesity. Annals of the Russian Academy of Medical Sciences. 2024;79(6):515-522. https://doi.org/10.15690/vramn18011. (In Russ.).
17. Fox CK, Barrientos-Pérez M, Bomberg EM, Dcruz J, Gies I, Harder-Lauridsen NM, Jalaludin MY, Sahu K, Weimers P, Zueger T, Arslanian S; SCALE Kids Trial Group. Liraglutide for Children 6 to <12 Years of Age with Obesity - A Randomized Trial. N Engl J Med. 2025;392(6):555-565. https://doi.org/10.1056/NEJMoa2407379.
18. Li Y, Rosenblit PD. Glucagon-Like Peptide-1 Receptor Agonists and Cardiovascular Risk Reduction in Type 2 Diabetes Mellitus: Is It a Class Effect? Curr Cardiol Rep. 2018 Sep 26;20(11):113. https://doi.org/10.1007/s11886-018-1051-2.
19. Gerstein HC, Colhoun HM, Dagenais GR, et al.; REWIND Trial Investigators. Design and baseline characteristics of participants in the Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial on the cardiovascular effects of dulaglutide. Diabetes Obes Metab. 2018 Jan;20(1):42-49. https://doi.org/10.1111/dom.13028.
20. Fisher M, Petrie MC, Ambery PD, et al. Cardiovascular safety of albiglutide in the Harmony programme: a meta-analysis. Lancet Diabetes Endocrinol. 2015 Sep;3(9):697-703. https://doi.org/10.1016/S2213-8587(15)00233-8.
21. Marso SP, Daniels GH, Brown-Frandsen K, et al.; LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2016 Jul 28;375(4):311-22. https://doi.org/10.1056/NEJMoa1603827.
22. Helmstädter J, Keppeler K, Aust F, et al. GLP-1 analog liraglutide improves vascular function in polymicrobial sepsis by reduction of oxidative stress and inflammation. Antioxidants. 2021;10(8):1175. https://doi.org/10.3390/antiox10081175.
23. Mehdi SF, Pusapati S, Anwar MS, et al. Glucagon-like peptide-1: a multifaceted anti-inflammatory agent. Frontiers in Immunology. 2023;14. https://doi.org/10.3389/fimmu.2023.1148209.
24. Bendotti G, Montefusco L, Lunati ME, et al. The anti-inflammatory and immunological properties of GLP-1 Receptor Agonists. Pharmacological Research. 2022;182:106320. https://doi.org/10.1016/j.phrs.2022.106320.
25. Халимов ЮШ, Агафонов ПВ, Кузьмич ВГ, Салухов ВВ. Агонисты рецепторов глюкогоноподобного пептида 1 типа и новые возможности первичной профилактики сердечно-сосудистых осложнений у больных сахарным диабетом 2 типа. Доктор. Ру / Khalimov YuSh, Agafonov PV, Kuzmich VG, Salukhov VV. Glucagon-like Peptide-1 Receptor Agonists and New Opportunities in Primary Prevention of Cardiovascular Complications in Patients with Type 2 Diabetes Mellitus. Doctor Ru. 2021;20(2):21-29. https://doi.org/10.31550/1727-2378-2021-20-2-21-29 (In Russ.).
26. Lu C, Xie T, Guo X, et al. Glucagon-like peptide-1 receptor agonist exendin-4 mitigates lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages. International Immunopharmacology. 2019;77:105969. https://doi.org/10.1016/j.intimp.2019.105969.
27. Diz-Chaves Y, Herrera-Pérez S, González-Matías LC, Mallo F. Effects of Glucagonlike peptide 1 (GLP-1) analogs in the hippocampus. Vitamins and Hormones. January 2022:457-478. https://doi.org/10.1016/bs.vh.2021.12.005.
28. Manavi MA. Neuroprotective effects of glucagon-like peptide-1 (GLP-1) analogues in epilepsy and associated comorbidities. Neuropeptides. 2022;94:102250. https://doi.org/10.1016/j.npep.2022.102250.
29. Cheng D, Yang S, Zhao X, Wang G. The role of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA) in Diabetes-Related Neurodegenerative Diseases. Drug Design Development and Therapy. 2022;Volume 16:665-684. https://doi.org/10.2147/dddt.s348055.
30. Shamkhalova MS, Sklyanik IA, Shestakova MV. Nephroprotective potential of glucagon-like peptide-1 receptor agonists. Diabetes Mellitus. 2020;23(1):56-64. https://doi.org/10.14341/dm12379.
31. Chen J, Zhao H, Ma X, et al. GLP-1/GLP-1R signaling in regulation of adipocyte differentiation and lipogenesis. Cellular Physiology and Biochemistry. 2017;42(3):11651176. https://doi.org/10.1159/000478872.
32. Balteau M, Van Steenbergen A, Timmermans AD, et al. AMPK activation by glucagonlike peptide-1 prevents NADPH oxidase activation induced by hyperglycemia in adult cardiomyocytes. AJP Heart and Circulatory Physiology. 2014;307(8):H1120-H1133. https://doi.org/10.1152/ajpheart.00210.2014.
33. Veprik A, Denwood G, Liu D, et al. Acetyl-CoA-carboxylase 1 (ACC1) plays a critical role in glucagon secretion. Communications Biology. 2022;5(1). https://doi.org/10.1038/s42003-022-03170-w.
34. Bu T, Sun Z, Pan Y, Deng X, Yuan G. Glucagon-Like peptide-1: new regulator in lipid metabolism. Diabetes & Metabolism Journal. 2024;48(3):354-372. https://doi.org/10.4093/dmj.2023.0277.
35. Gaspari T, Brdar M, Lee HW, et al. Molecular and cellular mechanisms of glucagon-like peptide-1 receptor agonist-mediated attenuation of cardiac fibrosis. Diabetes and Vascular Disease Research. 2015;13(1):56-68. https://doi.org/10.1177/1479164115605000.
Review
For citations:
Chubarov T.V., Esaulenko I.E., Peterkova V.A., Zhdanova O.A., Du W., Sharshova O.G. Study of mechanisms and approaches to incretin-based therapy for obesity in children. The Eurasian Journal of Life Sciences. 2025;1(1):43-52.
Views:
19
Email this article 