Abed MT, Al-Nimer MS, Al-Rawi KA (2014) The effect of short-term metformin therapy on insulin resistance among obese males in Al-Ramadi. Iraq Saudi J Obes 2(1):24–28. https://doi.org/10.4103/2347-2618.137594

Article  Google Scholar 

Allen KD, Thoma LM, Golightly YM (2022) Epidemiology of osteoarthritis. Osteoarthr Cartil 30(2):184–195. https://doi.org/10.1016/j.joca.2021.04.020

Article  CAS  Google Scholar 

Baeza-Flores GDC, Guzmán-Priego CG, Parra-Flores LI, Murbartián J, Torres-López JE, Granados-Soto V (2020) Metformin: a prospective alternative for the treatment of chronic pain. Front Pharmacol 11:558474. https://doi.org/10.3389/fphar.2020.558474

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bartels EM, Christensen R, Christensen P, Henriksen M, Bennett A, Gudbergsen H, Boesen M, Bliddal H (2014) Effect of a 16 weeks weight loss program on osteoarthritis biomarkers in obese patients with knee osteoarthritis: a prospective cohort study. Osteoarthr Cartil 22(11):1817–1825. https://doi.org/10.1016/j.joca.2014.07.027

Article  CAS  Google Scholar 

Belenska-Todorova L, Lambova SN, Stoyanova S, Georgieva E, Batsalova T, Moten D, Kolchakova D, Dzhambazov B (2021) Disease-modifying potential of metformin and alendronate in an experimental mouse model of osteoarthritis. Biomedicines 9(8):1017. https://doi.org/10.3390/biomedicines9081017

Article  PubMed  PubMed Central  Google Scholar 

Bierma-Zeinstra S (2019) Osteoarthritis. Lancet 393:1745–1759

Article  PubMed  Google Scholar 

Dougados M, Leclaire P, van der Heijde DMFM, Bloch DA, Bellamy N, Altman RD (2000) Response criteria for clinical trials on osteoarthritis of the knee and hip: a report of the osteoarthritis research society international standing committee for clinical trials response criteria initiative. Osteoarthr Cartil 8(6):395–403. https://doi.org/10.1053/joca.2000.0361

Article  CAS  Google Scholar 

Feng X, Pan J, Li J, Zeng C, Qi W, Shao Y, Liu X, Liu L, Xiao G, Zhang H, Bai X, Cai D (2020) Metformin attenuates cartilage degeneration in an experimental osteoarthritis model by regulating AMPK/mTOR. Aging (albany NY). 12(2):1087–1103

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gamze KUŞ, Yasaci Z, Canser BOZ, Türkmen E (2023) Association of osteoarthritis prevalence with age and obesity factors in oecd countries: panel regression model. Am J Phys Med Rehabil. https://doi.org/10.1097/PHM.0000000000002244

Article  Google Scholar 

Gregory EN, Codeluppi S, Gregory JA, Steinauer J, Svensson CI (2010) Mammalian target of rapamycin in spinal cord neurons mediates hypersensitivity induced by peripheral inflammation. Neuroscience 169(3):1392–1402. https://doi.org/10.1016/j.neuroscience.2010.05.067

Article  CAS  PubMed  Google Scholar 

Hao HQ, Zhang JF, He QQ, Wang Z (2019) Cartilage oligomeric matrix protein, C-terminal cross-linking telopeptide of type II collagen, and matrix metalloproteinase-3 as biomarkers for knee and hip osteoarthritis (OA) diagnosis: a systematic review and meta-analysis. Osteoarthr Cartil 27(5):726–736. https://doi.org/10.1016/j.joca.2018.10.009

Article  CAS  Google Scholar 

He Y, Ren E, Lu Z, Chen H, Qin Z, Wang J, He M, Liu G, Zheng L, Zhao J (2020) Rational engineering of ferritin nanocages for targeted therapy of osteoarthritis. Nanomed: Nanotechnol Biol Med. https://doi.org/10.1016/j.nano.2020.102210

Article  Google Scholar 

Hui F, Zhang Y, Ren T, Li X, Zhao M, Zhao Q (2019) Role of metformin in overweight and obese people without diabetes: a systematic review and network meta-analysis. Eur J Clin Pharmacol 75:437–450. https://doi.org/10.1007/s00228-018-2593-3

Article  PubMed  Google Scholar 

Lai FT, Yip BH, Hunter DJ, Rabago DP, Mallen CD, Yeoh EK, Wong SY, Sit RW (2022) Metformin use and the risk of total knee replacement among diabetic patients: a propensity-score-matched retrospective cohort study. Sci Rep 12(1):11571. https://doi.org/10.1038/s41598-022-15871-7

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lambova SN (2023a) Knee osteoarthritis—how close are we to disease-modifying treatment: emphasis on metabolic type knee osteoarthritis. Life 13(1):140. https://doi.org/10.3390/life13010140

Article  PubMed  PubMed Central  Google Scholar 

Lambova SN (2023b) Pleiotropic effects of metformin in osteoarthritis. Life 13(2):437. https://doi.org/10.3390/life13020437

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lambova SN, Ivanovska N, Stoyanova S, Belenska-Todorova L, Georgieva E, Batsalova T, Moten D, Apostolova D, Dzhambazov B (2023) Changes in the subchondral bone, visfatin, and cartilage biomarkers after pharmacological treatment of experimental osteoarthritis with metformin and alendronate. Int J Mol Sci 24(12):10103. https://doi.org/10.3390/ijms241210103

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li H, Ding X, Terkeltaub R, Lin H, Zhang Y, Zhou B, He K, Li K, Liu Z, Wei J, Yang Y, Xie H, Zeng C, Lei G (2020a) Exploration of metformin as novel therapy for osteoarthritis: preventing cartilage degeneration and reducing pain behavior. Arthritis Res Ther 22(1):1–11. https://doi.org/10.1186/s13075-020-2129-y

Article  CAS  Google Scholar 

Li J, Zhang B, Liu WX, Lu K, Pan H, Wang T, Yi D, Huang J, Zhao L, Ning G, Xing C, Xiao G, Feng S, Chen D (2020b) Metformin limits osteoarthritis development and progression through activation of AMPK signalling. Ann Rheum Dis. https://doi.org/10.1136/annrheumdis-2019-216713

Article  PubMed  Google Scholar 

Li H, Gou Y, Tian F, Zhang Y, Lian Q, Hu Y, Zhang L (2022) Combination of metformin and exercise alleviates osteoarthritis in ovariectomized mice fed a high-fat diet. Bone 157:116323. https://doi.org/10.1016/j.bone.2021.116323

Article  CAS  PubMed  Google Scholar 

Li D, Ruan G, Zhang Y, Zhao Y, Zhu Z, Ou Q, Huang H, Chen J, Han W, Tang S, Li J, Wang L, Chen T, Bai X, Cai D, Ding C (2023) Metformin attenuates osteoarthritis by targeting chondrocytes, synovial macrophages and adipocytes. Rheumatology 62(4):1652–1661. https://doi.org/10.1093/rheumatology/keac467

Article  PubMed  Google Scholar 

Lim YZ, Wang Y, Estee M, Abidi J, Kumar MU, Hussain SM, Wluka AE, Little CB, Cicuttini FM (2022) Metformin as a potential disease-modifying drug in osteoarthritis: a systematic review of pre-clinical and human studies. Osteoarthr Cartil 30(11):1434–1442. https://doi.org/10.1016/j.joca.2022.05.005

Article  CAS  Google Scholar 

Lu CH, Chung CH, Lee CH, Hsieh CH, Hung YJ, Lin FH, Tsao CH, Hsieh PS, Chien WC (2018) Combination COX-2 inhibitor and metformin attenuate rate of joint replacement in osteoarthritis with diabetes: a nationwide, retrospective, matched-cohort study in Taiwan. PLoS ONE 13(1):e0191242. https://doi.org/10.1371/journal.pone.0191242

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ma J, Zhang ZL, Hu XT, Wang XT, Chen AM (2018) Metformin promotes differentiation of human bone marrow derived mesenchymal stem cells into osteoblast via GSK3β inhibition. Eur Rev Med Pharmacol Sci. https://doi.org/10.26355/eurrev_201811_16424

Article  PubMed  Google Scholar 

Mai QG, Zhang ZM, Xu S, Lu M, Zhou RP, Zhao L, Jia CH, Wen ZH, Jin DD, Bai XC (2011) Metformin stimulates osteoprotegerin and reduces RANKL expression in osteoblasts and ovariectomized rats. J Cell Biochem 112(10):2902–2909. https://doi.org/10.1002/jcb.23206

Article  CAS  PubMed  Google Scholar 

McConnell S, Kolopack P, Davis AM (2001) The western ontario and mcmaster universities osteoarthritis index (WOMAC): a review of its utility and measurement properties. Arthr Care Res: off J Am Coll Rheumatol 45(5):453–461. https://doi.org/10.1002/1529-0131(200110)45:5%3c453::AID-ART365%3e3.0.CO;2-W

Article  CAS  Google Scholar 

Mohammed MM, Al-Shamma KJ, Jassim NA (2014) Evaluation of the clinical use of metformin or pioglitazone in combination with meloxicam in patients with knee osteoarthritis; using knee injury and osteoarthritis outcome score. Iraqi J Pharm Sci. 23(2):13–23

Google Scholar 

Na HS, Kwon JY, Lee SY, Lee SH, Lee AR, Woo JS, Jung K, Cho K-H, Choi J-W, Lee DH, Min H-K, Park S-H, Kim SJ, Cho ML (2021) Metformin attenuates monosodium-iodoacetate-induced osteoarthritis via regulation of pain mediators and the autophagy–lysosomal pathway. Cells 10(3):681. https://doi.org/10.3390/cells10030681

Article  CAS  PubMed  PubMed Central  Google Scholar