The effect of liraglutide on adipokine and incretin levels in children with obesity

Introduction. The prevalence of obesity in the pediatric population has reached epidemic proportions, necessitating the development of effective therapies. Studying the effect of pharmacotherapy on regulatory peptides such as adipokines and incretins is of significant scientific and practical interest.

Aim. To assess the dynamics of adipokine and incretin levels during 12-month therapy with the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide in children with obesity.

Materials and methods. A single- center prospective study included 20 children aged 12–18 years with obesity grades II–III and morbid obesity (SDS BMI ≥ 2.5). All patients received liraglutide at a standard dose of 3.0 mg for 12 months. Anthropometric parameters (body weight, SDS BMI) and levels of adipokines and incretins (leptin, spexin, ghrelin, obestatin, GLP-1, glucagon, glucose-dependent  insulinotropic polypeptide (GIP), glicentin, oxyntomodulin) were assessed before treatment, after 1, 4, and 12 months of therapy.

Results. Liraglutide therapy resulted in a significant reduction in body weight and SDS BMI (p < 0.05). A significant decrease in the concentration of spexin, glucagon-like peptide-1, and obestatin in blood plasma and an increase in the concentration of glucose-dependent  insulinotropic polypeptide and oxyntomodulin in blood serum were detected. Significant correlations were found between SDS BMI dynamics and levels of leptin (r = 0.558; p < 0.001), GLP-1 (r = 0.366; p = 0.026), and obestatin (r = -0.364; p = 0.023).

Conclusions. Liraglutide therapy leads not only to weight loss but also to significant changes in the adipokine and incretin profile in children with obesity. The dynamics of the studied biomarkers, particularly leptin, glucagon-like peptide-1, and obestatin, can be used to predict the effectiveness of glucagon-like peptide-1 analog therapy.

1. Romanitsa AI, Polyakov VM, Pogodina AV, Myasishchev NA, Klimkina YuN, Rychkova LV. Obese adolescent: social and psychological portrait. Acta Biomedica Scientifica. 2020;5(6):179–187. (In Russ.) https://doi.org/10.29413/ABS.2020-5.6.21.

2. Berezhnaya IV, Simakova MA, Zakharova IN. Obesity is an important paediatric problem that paediatricians and endocrinologists should address together. Pediatrics. Consilium Medicum. 2021;(4):346–350. (In Russ.) https://doi.org/10.26442/26586630.2021.4.201354.

3. Zorena K, Jachimowicz-Duda O, Slezak D, Robakowska M, Mrugacz M. Adipokines and obesity. Potential link to metabolic disorders and chronic complications. Int J Mol Sci. 2020;21(10):3570. https://doi.org/10.3390/ijms21103570.

4. Chan JL, Mantzoros CS. Leptin and the hypothalamic-pituitary regulation of the gonadotropin-gonadal axis. Pituitary. 2001;4(1-2):87–92. https://doi.org/10.1023/a:1012947113197.

5. Leinninger GM, Jo YH, Leshan RL, Louis GW, Yang H, Barrera JG et al. Leptin acts via leptin receptor-expressing lateral hypothalamic neurons to modulate the mesolimbic dopamine system and suppress feeding. Cell Metab. 2009;10(2):89–98. https://doi.org/10.1016/j.cmet.2009.06.011.

6. Li C, Friedman JM. Leptin receptor activation of SH2 domain containing protein tyrosine phosphatase 2 modulates Ob receptor signal transduction. Proc Natl Acad Sci U S A. 1999;96(17):9677–9682. https://doi.org/10.1073/pnas.96.17.9677.

7. Beltowski J. Leptin and atherosclerosis. Atherosclerosis. 2006;189(1):47–60. https://doi.org/10.1016/j.atherosclerosis.2006.03.003.

8. Ryzhov YR, Shpakov AO, Gzzyan AM. The role of leptin in the regulation of the reproductive system and prospects for its use in assisted reproductive technologies. Russian Journal of Human Reproduction. 2020;26(2):53–61. (In Russ.) https://doi.org/10.17116/repro20202602153.

9. Agarwal A, Durairajanayagam D, du Plessis SS. Utility of antioxidants during assisted reproductive techniques: an evidence based review. Reprod Biol Endocrinol. 2014;12:112. https://doi.org/10.1186/1477-7827-12-112.

10. Mills EG, Izzi-Engbeaya C, Abbara A, Comninos AN, Dhillo WS. Functions of galanin, spexin and kisspeptin in metabolism, mood and behaviour. Nat Rev Endocrinol. 2021;17(2):97–113. https://doi.org/10.1038/s41574-020-00438-1.

11. Petunina NA, Truhina LV, Siniсyna EI, Shestakova MV. Glucagon and α-cells as a novel therapeutic target in the management of diabetes mellitus. Diabetes Mellitus. 2013;16(3):35-40. (In Russ.) Available at: https://www.dia-endojournals.ru/jour/article/view/815.

12. Alexiadou K, Tan TM. Gastrointestinal peptides as therapeutic targets to mitigate obesity and metabolic syndrome. Curr Diab Rep. 2020;20(7):26. https://doi.org/10.1007/s11892-020-01309-9.

13. Holst JJ. The incretin system in healthy humans: The role of GIP and GLP-1. Metabolism. 2019;96:46–55. https://doi.org/10.1016/j.metabol.2019.04.014.

14. Romantsova TI. Glucagon-like peptide-1 analogue liraglutide (Saxenda®): mechanism of action, efficacy for the treatment of obesity. Obesity and Metabolism. 2018;15(1):3–11. (In Russ.) https://doi.org/10.14341/omet201813-11.

15. Raffort J, Lareyre F, Massalou D, Fénichel P, Panaïa-Ferrari P, Chinetti G. Insights on glicentin, a promising peptide of the proglucagon family. Biochem Med. 2017;27(2):308–324. https://doi.org/10.11613/BM.2017.034.

16. Holst JJ, Rosenkilde MM. Oxyntomodulin – past, present and future. Peptides. 2025;188:171393. https://doi.org/10.1016/j.peptides.2025.171393.

17. Ahmed MB, Habib AM, Badran S, Alsherawi A, Syed A, Khoogaly H et al. Spexin is a biomarker of the process that regulates leptin sensitivity. Peptides. 2025;190:171416. https://doi.org/10.1016/j.peptides.2025.171416.

18. Logvinova OV, Troshina EA. Prediction of early response to liraglutide therapy in patients with obesity. Obesity and Metabolism. 2020;17(1):3–12. (In Russ.) Available at: https://doi.org/10.14341/omet12274.

19. Логвинова ОВ, Галиева МО, Трошина ЕА, Мазурина НВ. Исходные уровни грелина и обестатина в плазме крови не предсказывают эффективность модификации образа жизни и терапии лираглутидом в суточной дозе 3,0 мг при первичном ожирении. В: Персонализированная медицина и практическое здравоохранение: сборник тезисов 8-го (26-го) Национального конгресса эндокринологов с международным участием, Москва, 22–25 мая 2019 г. М.: УП Принт; 2019. С. 315–316. Режим доступа: https://elibrary.ru/mufpzx.

20. Sklyanik IA, Shestakova MV. Prognostic factors for the carbohydrate metabolism normalization in patients with type 2 diabetes mellitus and obesity using liraglutide 3.0 mg per day. Terapevticheskii Arkhiv. 2021;93(10): 1203–1208. (In Russ.) https://doi.org/10.26442/00403660.2021.10.201070