{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T15:19:33Z","timestamp":1778858373453,"version":"3.51.4"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Inflammopharmacol"],"published-print":{"date-parts":[[2026,5]]},"DOI":"10.1007\/s10787-026-02218-1","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T08:15:14Z","timestamp":1777277714000},"page":"2843-2854","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metformin for knee osteoarthritis in overweight and obese adults: a systematic review and meta-analysis of efficacy, safety, and disease-modifying anti-inflammatory potential"],"prefix":"10.1007","volume":"34","author":[{"given":"Santenna","family":"Chenchula","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krishna Chaitanya","family":"Amerneni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Padmavathi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Anitha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohan Krishna","family":"Ghanta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shriraam","family":"Karunakaran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shubham","family":"Atal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunil","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pavani","family":"Saggurthi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shoibam","family":"Jenifa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. Mythili","family":"Bai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madhavrao","family":"Chavan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Balakrishnan","family":"Sadasivam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"issue":"1","key":"2218_CR1","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1186\/s13018-024-05120-0","volume":"19","author":"MS Abed","year":"2024","unstructured":"Abed MS, Aziz MZ, AbdelHamid NM, Soliman ES (2024) Effects of metformin phonophoresis and exercise therapy on pain, range of motion, and physical function in chronic knee osteoarthritis: a randomized clinical trial. J Orthop Surg Res 19(1):689. https:\/\/doi.org\/10.1186\/s13018-024-05120-0","journal-title":"J Orthop Surg Res"},{"issue":"4","key":"2218_CR2","doi-asserted-by":"publisher","first-page":"2349","DOI":"10.1007\/s10787-024-01495-y","volume":"32","author":"AE Aiad","year":"2024","unstructured":"Aiad AE, El Haggar SM, El Barbary AM, El Afify DR (2024) Metformin as adjuvant therapy in obese knee osteoarthritis patients. Inflammopharmacology 32(4):2349\u20132359. https:\/\/doi.org\/10.1007\/s10787-024-01495-y","journal-title":"Inflammopharmacology"},{"issue":"4","key":"2218_CR3","doi-asserted-by":"publisher","first-page":"4523","DOI":"10.1007\/s11033-024-05678-9","volume":"51","author":"AE Aiad","year":"2024","unstructured":"Aiad AE, El Haggar SM, El Barbary AM et al (2024) Metformin as adjuvant therapy in obese knee OA: effects on COMP, CTX-I and IL-1\u03b2. Mol Biol Rep 51(4):4523\u20134532. https:\/\/doi.org\/10.1007\/s11033-024-05678-9","journal-title":"Mol Biol Rep"},{"key":"2218_CR4","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s13075-023-03025-7","volume":"25","author":"N Alimoradi","year":"2023","unstructured":"Alimoradi N, Tahami M, Firouzabadi N, Haem E, Ramezani A (2023) Metformin attenuates symptoms of osteoarthritis: role of genetic diversity of BCL2 and CXCL16. Arthritis Res Ther 25:35. https:\/\/doi.org\/10.1186\/s13075-023-03025-7","journal-title":"Arthritis Res Ther"},{"issue":"1","key":"2218_CR5","doi-asserted-by":"publisher","DOI":"10.1002\/acr2.11755","volume":"7","author":"N Alimoradi","year":"2025","unstructured":"Alimoradi N, Ramezani A, Tahami M, Firouzabadi N (2025) Metformin exhibits anti-inflammatory effects by regulating microRNA-451\/CXCL16 and BCL-2 in patients with osteoarthritis. ACR Open Rheumatol 7(1):e11755","journal-title":"ACR Open Rheumatol"},{"key":"2218_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bbr.2015.12.012","volume":"301","author":"JS Allard","year":"2015","unstructured":"Allard JS, Perez EJ, Fukui K, Carpenter P, Ingram DK, de Cabo R (2015) Prolonged metformin treatment leads to reduced transcription of Nrf2 and neurotrophic factors without cognitive impairment in older mice. Behav Brain Res 301:1\u20139","journal-title":"Behav Brain Res"},{"issue":"3","key":"2218_CR7","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.3646","volume":"6","author":"MC Baker","year":"2023","unstructured":"Baker MC, Sheth K, Liu Y, Lu D, Lu R, Robinson WH (2023) Development of osteoarthritis in adults with type 2 diabetes treated with metformin versus sulfonylurea. JAMA Netw Open 6(3):e233646. https:\/\/doi.org\/10.1001\/jamanetworkopen.2023.3646","journal-title":"JAMA Netw Open"},{"issue":"6","key":"2218_CR8","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1016\/j.cmet.2016.05.011","volume":"23","author":"N Barzilai","year":"2016","unstructured":"Barzilai N, Crandall JP, Kritchevsky SB, Espeland MA (2016) Metformin as a tool to target aging. Cell Metab 23(6):1060\u20131065. https:\/\/doi.org\/10.1016\/j.cmet.2016.05.011","journal-title":"Cell Metab"},{"issue":"16","key":"2218_CR9","doi-asserted-by":"publisher","first-page":"4796","DOI":"10.3390\/jcm11164796","volume":"11","author":"S Chen","year":"2022","unstructured":"Chen S, Ruan G, Zeng M et al (2022) Metformin use and risk of total knee arthroplasty in knee osteoarthritis with diabetes or obesity. J Clin Med 11(16):4796. https:\/\/doi.org\/10.3390\/jcm11164796","journal-title":"J Clin Med"},{"issue":"11","key":"2218_CR10","doi-asserted-by":"publisher","DOI":"10.1111\/obr.13616","volume":"24","author":"S Chenchula","year":"2023","unstructured":"Chenchula S, Sharma S, Tripathi M, Chavan M, Misra AK, Rangari G (2023) Prevalence of overweight and obesity and their effect on COVID-19 severity and hospitalization: a systematic review and meta-analysis. Obes Rev 24(11):e13616. https:\/\/doi.org\/10.1111\/obr.13616","journal-title":"Obes Rev"},{"key":"2218_CR11","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1136\/bmj.315.7109.629","volume":"315","author":"M Egger","year":"1997","unstructured":"Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple graphical test. BMJ 315:629\u2013634. https:\/\/doi.org\/10.1136\/bmj.315.7109.629","journal-title":"BMJ"},{"issue":"2","key":"2218_CR12","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.18632\/aging.102635","volume":"12","author":"X Feng","year":"2020","unstructured":"Feng X, Pan J, Li J et al (2020) Metformin attenuates cartilage degeneration via AMPK\/mTOR signalling. Aging (Albany NY) 12(2):1087\u20131103. https:\/\/doi.org\/10.18632\/aging.102635","journal-title":"Aging (Albany NY)"},{"key":"2218_CR55","doi-asserted-by":"publisher","unstructured":"Feng J, Xiang J, Chen Y et al (2025) Metformin inhibits ferroptosis and alleviates chondrocyte imbalance in osteoarthritis models. Cell Death Dis 16:215. https:\/\/doi.org\/10.1038\/s41419-025-04210-x","DOI":"10.1038\/s41419-025-04210-x"},{"issue":"4","key":"2218_CR13","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1097\/XEB.0000000000000141","volume":"16","author":"L Furuya-Kanamori","year":"2018","unstructured":"Furuya-Kanamori L, Barendregt JJ, Doi SAR (2018) A new improved graphical and quantitative method for detecting bias in meta-analysis. Int J Evid Based Healthc 16(4):195\u2013203. https:\/\/doi.org\/10.1097\/XEB.0000000000000141","journal-title":"Int J Evid Based Healthc"},{"key":"2218_CR58","doi-asserted-by":"crossref","unstructured":"Gartlehner G, Dobrescu A, Evans TS et al (2015) Assessing the predictive validity of strength of evidence grades: a meta-epidemiological study. Agency for Healthcare Research and Quality (US)","DOI":"10.1016\/j.jval.2016.03.625"},{"key":"2218_CR61","doi-asserted-by":"crossref","unstructured":"Gomez R, Lago F, Gomez-Reino J, Dieguez C, Gualillo O (2009) Adipokines in the skeleton. J Mol Endocrinol 43:11\u201318","DOI":"10.1677\/JME-08-0131"},{"key":"2218_CR14","doi-asserted-by":"publisher","first-page":"1652732","DOI":"10.3389\/fmed.2025.1652732","volume":"12","author":"X Guo","year":"2025","unstructured":"Guo X, Xie H, Liu Y, Hou J, Tan H, Miao L, Xu Y, Tian Y (2025) The effect of metformin in clinical studies on knee osteoarthritis: an updated systematic review and meta-analysis. Front Med 12:1652732. https:\/\/doi.org\/10.3389\/fmed.2025.1652732","journal-title":"Front Med"},{"key":"2218_CR15","doi-asserted-by":"publisher","first-page":"1567544","DOI":"10.3389\/fphar.2025.1567544","volume":"16","author":"I Halabitska","year":"2025","unstructured":"Halabitska I, Petakh P, Kamyshnyi O (2025) Metformin as a disease-modifying therapy in osteoarthritis. Front Pharmacol 16:1567544. https:\/\/doi.org\/10.3389\/fphar.2025.1567544","journal-title":"Front Pharmacol"},{"issue":"5","key":"2218_CR16","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1302\/2046-3758.115.BJR-2021-0334.R1","volume":"11","author":"CP He","year":"2022","unstructured":"He CP, Chen C, Jiang XC et al (2022a) The role of advanced glycation end products in cartilage destruction in osteoarthritis. Bone Joint Res 11(5):292\u2013300. https:\/\/doi.org\/10.1302\/2046-3758.115.BJR-2021-0334.R1","journal-title":"Bone Joint Res"},{"key":"2218_CR17","doi-asserted-by":"publisher","first-page":"3012","DOI":"10.3390\/cells11193012","volume":"11","author":"M He","year":"2022","unstructured":"He M, Lu B, Opoku M et al (2022b) Metformin prevents or delays osteoarthritis progression: new insights and mechanisms. Cells 11:3012. https:\/\/doi.org\/10.3390\/cells11193012","journal-title":"Cells"},{"key":"2218_CR57","doi-asserted-by":"crossref","unstructured":"Higgins JPT, Thomas J, Chandler J et al (2019) Cochrane handbook for systematic reviews of interventions, 2nd edn. Wiley","DOI":"10.1002\/9781119536604"},{"issue":"Suppl 1","key":"2218_CR18","doi-asserted-by":"publisher","first-page":"S239","DOI":"10.1016\/j.joca.2023.01.490","volume":"31","author":"SR Jafarzadeh","year":"2023","unstructured":"Jafarzadeh SR, Peloquin CE, Felson DT (2023) Comparative effectiveness of metformin in preventing post-traumatic knee osteoarthritis. Osteoarthr Cartilage 31(Suppl 1):S239. https:\/\/doi.org\/10.1016\/j.joca.2023.01.490","journal-title":"Osteoarthr Cartilage"},{"issue":"7","key":"2218_CR19","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1007\/s40520-025-01541-2","volume":"37","author":"G Jiang","year":"2025","unstructured":"Jiang G, Yang X, Zhu G et al (2025) Comparative efficacy and safety of antidiabetic drugs in obese knee osteoarthritis patients: a network meta-analysis. Aging Clin Exp Res 37(7):1503\u20131515. https:\/\/doi.org\/10.1007\/s40520-025-01541-2","journal-title":"Aging Clin Exp Res"},{"key":"2218_CR50","doi-asserted-by":"crossref","unstructured":"Justice JN, Niedernhofer L, Robbins PD et al (2018) Development of clinical trials to extend healthy lifespan. Cardiovasc Endocrinol Metab 7(4):80\u201383","DOI":"10.1097\/XCE.0000000000000159"},{"issue":"5","key":"2218_CR20","doi-asserted-by":"publisher","first-page":"3195","DOI":"10.1007\/s10787-024-01558-0","volume":"32","author":"A Karim","year":"2024","unstructured":"Karim A, Waheed A, Ahmad F et al (2024) Metformin enhances physical performance in osteoarthritis with diabetes via zonulin reduction. Inflammopharmacology 32(5):3195\u20133203. https:\/\/doi.org\/10.1007\/s10787-024-01558-0","journal-title":"Inflammopharmacology"},{"issue":"10472","key":"2218_CR21","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/S0140-6736(24)02322-5","volume":"405","author":"M Kloppenburg","year":"2025","unstructured":"Kloppenburg M, Namane M, Roddy E (2025) Osteoarthritis. The Lancet 405(10472):71\u201385. https:\/\/doi.org\/10.1016\/S0140-6736(24)02322-5","journal-title":"The Lancet"},{"key":"2218_CR62","doi-asserted-by":"crossref","unstructured":"Lai FTT, Yip BHK, Hunter DJ et al (2022) Metformin use and total knee replacement risk in diabetes. Sci Rep 12:11571","DOI":"10.1038\/s41598-022-15871-7"},{"key":"2218_CR22","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s13075-020-2129-y","volume":"22","author":"H Li","year":"2020","unstructured":"Li H, Ding X, Terkeltaub R et al (2020a) Metformin prevents cartilage degeneration in osteoarthritis. Arthritis Res Ther 22:34. https:\/\/doi.org\/10.1186\/s13075-020-2129-y","journal-title":"Arthritis Res Ther"},{"issue":"5","key":"2218_CR23","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1136\/annrheumdis-2019-216713","volume":"79","author":"J Li","year":"2020","unstructured":"Li J, Zhang B, Liu WX et al (2020b) Metformin limits osteoarthritis progression via AMPK signalling. Ann Rheum Dis 79(5):635\u2013645. https:\/\/doi.org\/10.1136\/annrheumdis-2019-216713","journal-title":"Ann Rheum Dis"},{"issue":"4","key":"2218_CR24","doi-asserted-by":"publisher","first-page":"1652","DOI":"10.1093\/rheumatology\/keac467","volume":"62","author":"D Li","year":"2023","unstructured":"Li D, Ruan G, Zhang Y et al (2023) Metformin attenuates osteoarthritis by targeting chondrocytes, macrophages, and adipocytes. Rheumatology (Oxford) 62(4):1652\u20131661. https:\/\/doi.org\/10.1093\/rheumatology\/keac467","journal-title":"Rheumatology (Oxford)"},{"issue":"8","key":"2218_CR25","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1016\/j.joca.2022.02.008","volume":"30","author":"YZ Lim","year":"2022","unstructured":"Lim YZ, Wang Y, Estee MM et al (2022) Metformin as a potential disease-modifying drug in osteoarthritis: a systematic review of preclinical and human studies. Osteoarthr Cartilage 30(8):987\u2013998. https:\/\/doi.org\/10.1016\/j.joca.2022.02.008","journal-title":"Osteoarthr Cartilage"},{"issue":"1","key":"2218_CR26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0191242","volume":"13","author":"CH Lu","year":"2018","unstructured":"Lu CH, Chung CH, Lee CH et al (2018) Combination COX-2 inhibitor and metformin attenuates the rate of joint replacement in osteoarthritis with diabetes. PLoS ONE 13(1):e0191242. https:\/\/doi.org\/10.1371\/journal.pone.0191242","journal-title":"PLoS ONE"},{"key":"2218_CR65","doi-asserted-by":"crossref","unstructured":"Martin-Montalvo A, Mercken EM, Mitchell SJ et al (2013) Metformin improves healthspan and lifespan in mice. Nat Commun 4:2192","DOI":"10.1038\/ncomms3192"},{"key":"2218_CR59","unstructured":"Mohammed M, Al-Shamma K, Jassim N (2014) Evaluation of metformin or pioglitazone in combination with meloxicam in knee osteoarthritis. Iraqi J Pharm Sci"},{"key":"2218_CR53","unstructured":"National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (2025) Osteoarthritis. https:\/\/www.niams.nih.gov\/health-topics\/osteoarthritis. Accessed Oct 2025"},{"key":"2218_CR56","doi-asserted-by":"publisher","unstructured":"Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A (2016) Rayyan\u2014a web and mobile app for systematic reviews. System Rev 5:210. https:\/\/doi.org\/10.1186\/s13643-016-0384-4","DOI":"10.1186\/s13643-016-0384-4"},{"issue":"372","key":"2218_CR27","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71.PMID:33782057;PMCID:PMC8005924","volume":"29","author":"MJ Page","year":"2021","unstructured":"Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD et al (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 29(372):n71. https:\/\/doi.org\/10.1136\/bmj.n71.PMID:33782057;PMCID:PMC8005924","journal-title":"BMJ"},{"issue":"20","key":"2218_CR28","doi-asserted-by":"publisher","first-page":"1804","DOI":"10.1001\/jama.2025.3471","volume":"333","author":"F Pan","year":"2025","unstructured":"Pan F, Wang Y, Lim YZ et al (2025) Metformin for knee osteoarthritis with overweight or obesity: a randomized clinical trial. JAMA 333(20):1804\u20131812. https:\/\/doi.org\/10.1001\/jama.2025.3471","journal-title":"JAMA"},{"key":"2218_CR29","doi-asserted-by":"publisher","first-page":"127","DOI":"10.4049\/jimmunol.1800006","volume":"203","author":"MJ Park","year":"2019","unstructured":"Park MJ, Moon SJ, Baek JA et al (2019) Metformin augments anti-inflammatory and chondroprotective properties of mesenchymal stem cells in experimental osteoarthritis. J Immunol 203:127\u2013136. https:\/\/doi.org\/10.4049\/jimmunol.1800006","journal-title":"J Immunol"},{"key":"2218_CR30","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.952560","volume":"13","author":"Y Song","year":"2022","unstructured":"Song Y, Wu Z, Zhao P (2022) The effects of metformin in the treatment of osteoarthritis: current perspectives. Front Pharmacol 13:952560","journal-title":"Front Pharmacol"},{"key":"2218_CR54","doi-asserted-by":"publisher","unstructured":"Song M, Chen H, Li J et al (2023) Comparison of the burden of knee osteoarthritis due to high BMI in China and globally. Ann Rheum Dis 82(11):1422\u20131429. https:\/\/doi.org\/10.1136\/annrheumdis-2023-224567","DOI":"10.1136\/annrheumdis-2023-224567"},{"key":"2218_CR52","doi-asserted-by":"publisher","unstructured":"Steinmetz JD, Culbreth GT, Haile LM et al (2023) Global, regional, and national burden of osteoarthritis, 1990\u20132020 and projections to 2050: a systematic analysis for the global burden of disease study 2021. Lancet Rheumatol 5(9):e508\u2013e522. https:\/\/doi.org\/10.1016\/S2665-9913(23)00163-7","DOI":"10.1016\/S2665-9913(23)00163-7"},{"issue":"1","key":"2218_CR31","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1038\/s41572-025-00594-6","volume":"11","author":"S Tang","year":"2025","unstructured":"Tang S, Zhang C, Oo WM et al (2025) Osteoarthritis. Nat Rev Dis Primers 11(1):10. https:\/\/doi.org\/10.1038\/s41572-025-00594-6","journal-title":"Nat Rev Dis Primers"},{"issue":"32s","key":"2218_CR32","doi-asserted-by":"crossref","first-page":"5493","DOI":"10.63682\/jns.v14i32S.7965","volume":"14","author":"S Varshini","year":"2025","unstructured":"Varshini S, Karthickeyan K, Shanmugasundaram P (2025) Effect of metformin in obese knee osteoarthritis patients. J Neonatal Surg 14(32s):5493\u20135502","journal-title":"J Neonatal Surg"},{"key":"2218_CR33","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.cytogfr.2018.10.002","volume":"44","author":"T Wang","year":"2018","unstructured":"Wang T, He C (2018) Pro-inflammatory cytokines: the link between obesity and osteoarthritis. Cytokine Growth Factor Rev 44:38\u201350. https:\/\/doi.org\/10.1016\/j.cytogfr.2018.10.002","journal-title":"Cytokine Growth Factor Rev"},{"key":"2218_CR34","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1186\/s13075-019-1915-x","volume":"21","author":"Y Wang","year":"2019","unstructured":"Wang Y, Hussain SM, Wluka AE et al (2019) Association between metformin use and disease progression in obese people with knee osteoarthritis. Arthritis Res Ther 21:127. https:\/\/doi.org\/10.1186\/s13075-019-1915-x","journal-title":"Arthritis Res Ther"},{"key":"2218_CR64","doi-asserted-by":"crossref","unstructured":"Xu T, Liu K, Fan J et al (2024) Metformin mitigates osteoarthritis progression via PI3K\/AKT\/mTOR pathway. Open Life Sci 19:20220922","DOI":"10.1515\/biol-2022-0922"},{"key":"2218_CR35","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1186\/s13018-023-03571-5","volume":"18","author":"S Yan","year":"2023","unstructured":"Yan S, Dong W, Li Z et al (2023) Metformin regulates chondrocyte senescence via miR-34a\/SIRT1 in osteoarthritis. J Orthopedic Surg Res 18:198. https:\/\/doi.org\/10.1186\/s13018-023-03571-5","journal-title":"J Orthopedic Surg Res"},{"key":"2218_CR51","doi-asserted-by":"publisher","unstructured":"Yang S, Zhou L, Gong W, Guo B, Wang L (2024) Global burden of osteoarthritis from 1990 to 2019 attributable to high body mass index. Arch Med Sci 20(6):1841\u20131853. https:\/\/doi.org\/10.5114\/aoms\/187150","DOI":"10.5114\/aoms\/187150"},{"key":"2218_CR36","unstructured":"Yao K, Yue C, Li Y, Li F, Wang Q et al. (2025) Association of metformin use with osteoarthritis incidence, progression, and joint arthroplasty risk in the knee and hip: a systematic review and meta-analysis. J Arthroplasty"},{"key":"2218_CR63","doi-asserted-by":"crossref","unstructured":"Ye M, Vena JE, Shen-Tu G et al (2025) Metformin use and risk of total joint replacement in patients with diabetes. BMC Musculoskelet Disord 26:312","DOI":"10.1186\/s12891-025-08562-7"},{"issue":"11","key":"2218_CR37","doi-asserted-by":"publisher","first-page":"1506","DOI":"10.1016\/j.joca.2022.06.010","volume":"30","author":"Y Zhang","year":"2022","unstructured":"Zhang Y, Li D, Zhu Z et al (2022) Evaluating the impact of metformin targets on osteoarthritis risk: a Mendelian randomization study. Osteoarthr Cartilage 30(11):1506\u20131514. https:\/\/doi.org\/10.1016\/j.joca.2022.06.010","journal-title":"Osteoarthr Cartilage"},{"issue":"6","key":"2218_CR38","doi-asserted-by":"publisher","first-page":"5355","DOI":"10.3390\/ijms24065355","volume":"24","author":"M Zheng","year":"2023","unstructured":"Zheng M, Zhu Y, Wei K et al (2023) Metformin attenuates synovial M1 macrophage polarization in osteoarthritis. Int J Mol Sci 24(6):5355. https:\/\/doi.org\/10.3390\/ijms24065355","journal-title":"Int J Mol Sci"},{"key":"2218_CR39","doi-asserted-by":"publisher","first-page":"E1672","DOI":"10.1503\/cmaj.220952","volume":"194","author":"Z Zhu","year":"2022","unstructured":"Zhu Z, Huang JY, Ruan G et al (2022) Metformin use and associated risk of total joint replacement in patients with type 2 diabetes. CMAJ 194:E1672\u2013E1684. https:\/\/doi.org\/10.1503\/cmaj.220952","journal-title":"CMAJ"},{"key":"2218_CR60","doi-asserted-by":"crossref","unstructured":"Zhuo Q, Yang W, Chen J, Wang Y (2012) Metabolic syndrome meets osteoarthritis. Nat Rev Rheumatol 8:729","DOI":"10.1038\/nrrheum.2012.135"}],"container-title":["Inflammopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10787-026-02218-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10787-026-02218-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10787-026-02218-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T15:01:23Z","timestamp":1778857283000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10787-026-02218-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,27]]},"references-count":55,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["2218"],"URL":"https:\/\/doi.org\/10.1007\/s10787-026-02218-1","relation":{},"ISSN":["0925-4692","1568-5608"],"issn-type":[{"value":"0925-4692","type":"print"},{"value":"1568-5608","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,27]]},"assertion":[{"value":"11 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Not Applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}