Новые возможности использования гипогликемических препаратов в лечении остеоартрита: ОБЗОРЫ

Анна Сергеевна  Мерлушкина; Ангелина Ивановна   Жигулина; Виктор Николаевич  Федорец; Владимир Станиславович  Василенко

doi:10.56871/MTP.2026.18.17.008

New possibilities of using hypoglycemic drugsin the treatment of osteoarthritis

REVIEWS

Anna S. Merlushkina Kirov Military Medical Academy, 6Zh Akademika Lebedeva str., Saint Petersburg, 194044, Russian Federation https://orcid.org/0009-0007-3893-7383
Angelina I. Zhigulina Kirov Military Medical Academy, 6Zh Akademika Lebedeva str., Saint Petersburg, 194044, Russian Federation https://orcid.org/0000-0002-7850-1783
Viktor N. Fedorets Saint Petersburg State Pediatric Medical University, 2 Litovskaya str., Saint Petersburg, 194100, Russian Federation
Vladimir S. Vasilenko Saint Petersburg State Pediatric Medical University, 2 Litovskaya str., Saint Petersburg, 194100, Russian Federation https://orcid.org/0000-0002-8833-304X

Keywords:

osteoarthritis glucagon-like peptide 1 dipeptidyl peptidase 4 inhibitors sodium-glucose co-transporter type 2 inhibitors Liraglutide Empagliflozin остеоартрит глюкагоноподобный пептид-1 ингибиторы дипептидилпептидазы-4 ингибиторы натрий-глюкозного котранспортера 2-го типа лираглутид эмпаглифлозин

Abstract

Osteoarthritis is the most common and debilitating joint disease with limited physical activity and reduced quality of life in adults. This disease is socially significant, as it leads to disability of the population, and even to disability. Over the past 10 years, the incidence has increased by 2 times and continues to grow steadily. Patients with OA have high comorbidity and low physical activity. The basis of osteoarthritis treatment includes physical exercise, weight loss in combination with the use of basic osteoarthritis therapy, the choice of which is based on the phenotype of the disease and comorbid conditions. But at the same time, the exact mechanism of osteoatritis is not known, which means that there is no pathogenetic treatment. Recent studies have revealed a common occurrence of metabolic diseases, such as diabetes mellitus, and metabolic disorders in the tissues of the joint. This allows us to consider sugar-lowering therapy as a possible treatment for osteoarthritis. Preparations of the glucagon-like peptide-1 group have proven themselves to be effective in weight loss, which is a significant factor in the occurrence of joint damage. In addition, the pleiotropic anti-inflammatory effect of these drugs was found. Glucagon-like peptide agonists are the most studied class of hypoglycemic agents. A similar effect was observed in dipeptidyl peptidase-4 inhibitors. Moreover, the possibility of using the receptors of this enzyme as an extracellular marker of cell aging has been considered in animal models. The youngest and most promising class of hypoglycemic drugs are sodium-glucose co-transporter type 2 inhibitors. Their possibilities of suppressing various mechanisms of suppressing inflammation in the cells and tissues of joints are considered. The anti-inflammatory effect was achieved due to a violation of the mechanism of assembly and activation of inflammasomes, protein complexes that trigger the production of inflammatory mediators in cells. However, these properties require further study. This review shows the prospects of using different classes of hypoglycemic drugs in the treatment of osteoarthritis.

Author Biographies

Anna S. Merlushkina, Kirov Military Medical Academy, 6Zh Akademika Lebedeva str., Saint Petersburg, 194044, Russian Federation

6th-year cadet of the Faculty of Training Doctors for the Navy

Angelina I. Zhigulina, Kirov Military Medical Academy, 6Zh Akademika Lebedeva str., Saint Petersburg, 194044, Russian Federation

Cand. Sci. (Med.), Associate Professor, Department of Faculty Therapy

Viktor N. Fedorets, Saint Petersburg State Pediatric Medical University, 2 Litovskaya str., Saint Petersburg, 194100, Russian Federation

Dr. Sci. (Med.), Professor of the Department of Hospital Therapy with a Course in Endocrinology

Vladimir S. Vasilenko, Saint Petersburg State Pediatric Medical University, 2 Litovskaya str., Saint Petersburg, 194100, Russian Federation

Dr. Sci.(Med.), Professor, Head of the Department of Hospital Therapy with a Course in Endocrinology

References

1. Алексеева Л.И., Таскина Е.А., Кашеварова Н.Г. Остеоартрит: эпидемиология, классификация, факторы риска и прогрессирования, клиника, диагностика, лечение. Сов pe менная ревматология. 2019.(2):9–21. https://doi.org/10.26442/00403660.2019.05.000194.

2. Алексеева Л.И., Телышев К.А. Ранний остеоартрит: разработка критериев диагностики. Современная ревматология. 2020. 14(3):140–145. https://doi.org/10.14412/1996-7012-2020-3-140-145.

3. Журавлева Л.В., Олейник М.А. Влияние сахарного диабета 2 типа и ожирения на клинические проявления остеоартроза и связь их с цитокинами. Научные ведомости Белгородского государственного университета. 2015. 207(10):26–34.

4. Hunter D.J., Bierma-Zeinstra S. Osteoarthritis. Lancet. 2019. 393(10182):1745–1759. https://doi.org/10.1016/S0140-6736(19)30417-9.

5. Каратеев А.Е., Лила А.М. Остеоартрит: современная клиническая концепция и некоторые перспективные терапевтические подходы. Научно - практическая ревматология. 2018; 56(1):70–81.

6. Портянникова О.О., Цвингер С.М., Говорин А.В., Романова Е.Н. Анализ распространенности и факторов риска развития остеоартрита коленного сустава в популяции. Сов pe менная ревматология. 2019. 13(2):105–111.

7. Алексеева Л.И., Таскина Е.А., Кашеварова Н.Г. и др. Остеоартрит коленных суставов и метаболический синдром: новые подходы к терапии. Научно - практическая ревматология. 2018. 56(2):157–163.

8. Weng Q., Chen Q., Jiang T., Zhang Y., Zhang W., Doherty M. et al. Global burden of early-onset osteoarthritis, 1990–2019: Results from the Global Burden of Disease Study 2019. Ann Rheum Dis. 2024. 83(7):915–925. https://doi.org/10.1136/ard-2023-225324.

9. Чилилов А.М., Оськов Ю.И., Зеленова О.В., Абрамов С.И. Анализ эпидемиологических показателей остеоартрозов по данным форм государственного статистического наблюдения за период 2017–2021 годы в Российской Федерации. Современные проблемы здравоохранения и медицинской статистики. 2023. (2):124–139.

10. Oren T.W., Botolin S., Williams A., Bucknell A., King K.B. Arthroplasty in veterans: analysis of cartilage, bone, serum, and synovial fluid reveals differences and similarities in osteoarthritis with and without comorbid diabetes. J Rehabil Res Dev. 2011. 48(10):1195–210. https://doi.org/10.1682/jrrd.2010.09.0186.

11. Zhuo Q.I., Yang W., Chen J., Wang Y. Metabolic syndrome meets osteoarthritis. Nat Rev Rheumatol. 2012. 8(12):729–737. https://doi.org/10.1038/nrrheum.2012.135.

12. Красивина И.Г., Долгова Л.Н., Носкова А.С., Лаврухина А.А., Заводчиков А.А. Влияние сахарного диабета 2 типа на проявления гонартроза. Сахарный диабет. 2007. 10(3):24–26. https://doi.org/10.14341/2072-0351-5993.

13. Лаврухина А.А. Особенности поражения суставов при сахарном диабете: дис. … канд. мед. наук. Ярославль. 2004.

14. Leaverton P.E., Peregoy J., Fahlman L., Sangeorzan E., Barrett J.P. Jr. Does diabetes hide osteoarthritis pain? Med Hypotheses. 2012. 78(4):471–474. https://doi.org/10.1016/j.mehy.2012.01.008.

15. Nah S.S., Choi I.Y., Lee C.K., Oh J.S., Kim Y.G. et al. Effects of advanced glycation end products on the expression of COX-2, PGE2 and NO in human osteoarthritic chondrocytes. Rheumatology (Oxford). 2008. 47(4):425–431. https://doi.org/10.1093/rheumatology/kem376.

16. Laiguillon M.C., Courties A., Houard X., Auclair M., Sautet A. et al. Characterization of diabetic osteoarthritic cartilage and role of high glucose environment on chondrocyte activation: Toward pathophysiological delineation of diabetes mellitus-related osteoarthritis. Osteoarthritis Cartilage. 2015. 23(9):1513–1522. https://doi.org/10.1016/j.joca.2015.04.026.

17. Courties A., Berenbaum F., Sellam J. The phenotypic approach to osteoarthritis: A look at metabolic syndrome - associated osteoarthritis. Joint Bone Spine. 2019. 86(6):725–730. https://doi.org/10.1016/j.jbspin.2018.12.005.

18. Cornu M., Modi H., Kawamori D., Kulkarni R.N., Joffraud M., Thorens B. Glucagon - like peptide-1 increases beta - cell glucose competence and proliferation by translational induction of insulin - like growth factor-1 receptor expression. J Biol Chem. 2010. 285(14):10538–10545. https://doi.org/10.1074/jbc.M109.091116.

19. Chen J., Xie J.J., Shi K.S. et al. Glucagon - like peptide-1 receptor regulates endoplasmic reticulum stress - induced apoptosis and the associated inflammatory response in chondrocytes and the progression of osteoarthritis in rat. Cell Death Dis. 2018. 9(2):212. https://doi.org/10.1038/s41419-017-0217-y.

20. Jamal N., Hollabaugh W., Scott L., Takkouche S. Unravelling the ties that bind: The intersection of obesity, osteoarthritis, and inflammatory pathways with emphasis on glucagon ‐ like peptide‐1 agonists. Clin Obes. 2025. 15(1):e12700. https://doi.org/10.1111/cob.12700.

21. Meurot C., Martin C., Sudre L. et al. Liraglutide, a glucagon - like peptide 1 receptor agonist, exerts analgesic, anti - inflammatory and anti - degradative actions in osteoarthritis. Sci Rep. 2022. 12(1):1567. https://doi.org/10.1038/s41598-022-05323-7.

22. Samajdar S.S., Bhaduri G., Ghoshal P.K., Mukherjee S., Pal J. et al. Dual effects of dulaglutide on glycemic control and knee osteoarthritis pain in elderly patients with type 2 diabetes. Pain Manag. 2024. 14(7):365–373. https://doi.org/10.1080/17581869.2024.2402214.

23. Gudbergsen H., Overgaard A., Henriksen M., Wæhrens E.E., Bliddal H. et al. Liraglutide after diet - induced weight loss for pain and weight control in knee osteoarthritis: a randomized controlled trial. Am J Clin Nutr. 2021. 113(2): 314–323. https://doi.org/10.1016/j.ajcnut.2025.07.013.

24. Deacon C.F. Dipeptidyl peptidase‐4 inhibitors in the treatment of type 2 diabetes: a comparative review. Diabetes, Obesity and Metabolism. 2011. 13(1):7–18. https://doi.org/10.1111/j.1463-1326.2010.01306.

25. Kim K.M., Noh J.H., Bodogai M., Martindale J.L., Yang X., Indig F.E. et al. Identification of senescent cell surface targetable protein DPP4. Genes Dev. 2017. 31(15):1529–1534. https://doi.org/10.1101/gad.302570.117.

26. Chen Y.H., Byers Kraus V., Chang Y.S. et al. Dipeptidyl - peptidase 4 inhibitors reduce the incidence of total hip replacement and total knee replacement in type 2 diabetes mellitus patients. Osteoarthritis and Cartilage. 2024. 32:S182.

27. Ro D.H., Cho G.H., Kim J.Y., Min S.K., Yang H.R. et al. Selective targeting of dipeptidyl ‐ peptidase 4 (D P P ‐ 4) positive senescent chondrocyte ameliorates osteoarthritis progression. Aging Cell. 2024. 23(7):e14161. https://doi.org/10.1111/acel.14161.

28. Mohetaer M., Li G., Wang Y., Cao L. Protective effects of gemigliptin against type II collagen degradation in human chondrocytes. Biomed Pharmacother. 2018. 104:590–594. https://doi.org/10.1016/j.biopha.2018.04.018.

29. Wang T., Yang L., Liang Z., Wang L., Su F., Wang X. et al. Targeting cellular senescence prevents glucocorticoid-induced bone loss through modulation of the DPP4-GLP-1 axis. Signal Transduct Target Ther. 2021. 6(1):143. https://doi.org/10.1038/s41392-021-00528-0.

30. Rajasekeran H., Lytvyn Y., Cherney D.Z. Sodium - glucose cotransporter 2 inhibition and cardiovascular risk reduction in patients with type 2 diabetes: the emerging role of natriuresis. Kidney Int. 2016. 89(3):524–526. https://doi.org/10.1016/j.kint.2015.12.038.

31. Benetti E., Mastrocola R., Vitarelli G. et al. Empagliflozin protects against diet - induced NLRP-3 inflammasome activation and lipid accumulation. J Pharmacol Exp Ther. 2016. 359(1):45–53. https://doi.org/10.1124/jpet.116.235069.

32. Lee N., Heo Y.J., Choi S.E., Jeon J.Y., Han S.J., Kim D.J. et al. Anti ‐ inflammatory effects of empagliflozin and gemigliptin on L P S ‐ stimulated macrophage via the IKK/NF‐κB, MKK7/JNK, and JAK2/STAT1 signalling pathways. J Immunol Res. 2021. 2021(1):9944880. https://doi.org/10.1155/2021/9944880.

33. Ru B., Chen Zh., Xu L., Li Sh., Cai W. Empagliflozin ameliorated chondrocytes inflammation, catabolism and senescence and osteoarthritis via suppressing the nuclear factor kappa-B signal pathway. Authorea. 2024. https://doi.org/10.22541/au.170663701.19667866/v1.

New possibilities of using hypoglycemic drugsin the treatment of osteoarthritis: REVIEWS. (2026). Medicine: Theory and Practice, 11(1), 94-103. https://doi.org/10.56871/MTP.2026.18.17.008

Download Citation

How to Cite