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These individuals have many other shared metabolic risk factors. Metformin is a safe, inexpensive, well-tolerated drug that has pleiotropic effects, including structural protection, anti-inflammatory and analgesic effects in OA, specifically the knee. The aim of this randomised, double-blind, placebo-controlled trial is to determine whether metformin reduces knee pain over 6 months in individuals with symptomatic knee OA who are overweight or obese.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>One hundred and two participants with symptomatic knee OA and overweight or obesity will be recruited from the community in Melbourne, Australia, and randomly allocated in a 1:1 ratio to receive either metformin 2\u2009g or identical placebo daily for 6 months. The primary outcome is reduction of knee pain [assessed by 100\u2009mm Visual Analogue Scale (VAS)] at 6 months. The secondary outcomes are OMERACT-OARSI (Outcome Measures in Rheumatology-Osteoarthritis Research Society International) responder criteria [Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, function and participant\u2019s global assessment (VAS)] at 6 months; change in knee pain, stiffness, function using WOMAC at 6 months and quality of life at 6 months. Adverse events will be recorded. The primary analysis will be by intention to treat, including all participants in their randomised groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethics approval has been obtained from the Alfred Hospital Ethics Committee (708\/20) and Monash University Human Research Ethics Committee (28498). Written informed consent will be obtained from all the participants. The findings will be disseminated through peer-review publications and conference presentations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>ACTRN12621000710820 .<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2023-079489","type":"journal-article","created":{"date-parts":[[2023,12,9]],"date-time":"2023-12-09T13:23:43Z","timestamp":1702128223000},"page":"e079489","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Metformin for knee osteoarthritis with obesity: study protocol for a randomised, double-blind, placebo-controlled trial"],"prefix":"10.1136","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6960-8813","authenticated-orcid":false,"given":"Yuan Z","family":"Lim","sequence":"first","affiliation":[{"name":"School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7629-4178","authenticated-orcid":false,"given":"Yuanyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna M.","family":"Urquhart","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4714-7195","authenticated-orcid":false,"given":"Mahnuma Mahfuz","family":"Estee","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita E","family":"Wluka","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephane","family":"Heritier","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8200-1618","authenticated-orcid":false,"given":"Flavia M","family":"Cicuttini","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,12,9]]},"reference":[{"key":"2025121220570635000_13.12.e079489.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30925-9"},{"key":"2025121220570635000_13.12.e079489.2","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.j1131","article-title":"Impact of total knee replacement practice: cost effectiveness analysis of data from the osteoarthritis initiative","volume":"356","author":"Ferket","year":"2017","journal-title":"BMJ"},{"key":"2025121220570635000_13.12.e079489.3","doi-asserted-by":"crossref","DOI":"10.1186\/s12891-019-2411-9","article-title":"The projected burden of primary total knee and hip replacement for osteoarthritis in Australia to the year 2030","volume":"20","author":"Ackerman","year":"2019","journal-title":"BMC Musculoskelet Disord"},{"key":"2025121220570635000_13.12.e079489.4","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.joca.2015.01.006","article-title":"Clinical phenotypes in patients with knee osteoarthritis: a study in the Amsterdam osteoarthritis cohort","volume":"23","author":"van der Esch","year":"2015","journal-title":"Osteoarthr Cartil"},{"key":"2025121220570635000_13.12.e079489.5","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1002\/acr.20571","article-title":"Identification of phenotypes with different clinical outcomes in knee osteoarthritis: data from the osteoarthritis initiative","volume":"63","author":"Knoop","year":"2011","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"2025121220570635000_13.12.e079489.6","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keu464"},{"key":"2025121220570635000_13.12.e079489.7","doi-asserted-by":"publisher","DOI":"10.3810\/pgm.2009.11.2073"},{"key":"2025121220570635000_13.12.e079489.8","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0b013e32835a9414"},{"key":"2025121220570635000_13.12.e079489.9","doi-asserted-by":"crossref","unstructured":"Rojas LBA , Gomes MB . 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