{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T18:15:46Z","timestamp":1783016146636,"version":"3.54.6"},"reference-count":23,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82572715"],"award-info":[{"award-number":["82572715"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Orthopaedic Surgery"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Postoperative inflammation and pain remain key barriers to recovery after total knee arthroplasty (TKA). Metformin has anti\u2010inflammatory properties, but its perioperative impact in TKA is unclear. This study evaluated whether regular metformin use reduces postoperative inflammation and pain in T2DM patients undergoing TKA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this single\u2010center retrospective cohort study, patients with Type 2 diabetes mellitus (T2DM) who underwent primary TKA between December 2024 and May 2025 were included. Patients were grouped based on whether they had regularly taken metformin. 1:1 propensity score matching was performed to reduce baseline differences between groups, yielding 60 matched pairs. Inflammatory markers including C\u2010reactive protein (CRP), interleukin\u20106 (IL\u20106), erythrocyte sedimentation rate (ESR), and D\u2010dimer were measured preoperatively and on postoperative days 1 and 3. Pain was assessed using the Visual Analogue Scale (VAS) on postoperative days 1 and 3. Linear mixed\u2010effects models were used to compare outcomes between groups after adjusting for residual confounders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In the matched cohort, the metformin group showed significantly lower CRP levels on postoperative day 3 (107.04\u2009\u00b1\u200949.19 vs. 130.91\u2009\u00b1\u200959.62\u2009mg\/L,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.02), lower IL\u20106 levels on postoperative day 1 (62.22\u2009\u00b1\u200947.17 vs. 91.07\u2009\u00b1\u200941.55\u2009pg\/mL,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01), and postoperative day 3 (31.33\u2009\u00b1\u200920.84 vs. 57.74\u2009\u00b1\u200959.98\u2009pg\/mL,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01), and lower ESR levels on postoperative day 3 (45.40\u2009\u00b1\u200917.85 vs. 47.05\u2009\u00b1\u200920.19\u2009mm\/h,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03) than the non\u2010metformin group. VAS pain scores on postoperative day 3 were also significantly lower in the metformin group (3.03\u2009\u00b1\u20091.03 vs. 4.15\u2009\u00b1\u20091.25,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). These differences remained significant after adjusting for confounders.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Long\u2010term regular use of metformin is associated with reduced acute inflammation and postoperative pain in T2DM patients undergoing TKA. As a widely used and well\u2010tolerated medication, metformin holds promise as a low\u2010cost, adjunctive therapeutic strategy to enhance early recovery and improve perioperative outcomes in diabetic patients undergoing TKA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/os.70352","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T12:52:32Z","timestamp":1780491152000},"page":"1368-1374","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metformin Use Is Associated With Reduced Inflammation and Pain After Total Knee Arthroplasty in Patients With Type 2 Diabetes"],"prefix":"10.1111","volume":"18","author":[{"given":"Zhongyu","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Orthopedics Peking Union Medical College Hospital  Beijing People's Republic of China"},{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Peking Union Medical College and Chinese Academy of Medical Sciences  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery Peking Union Medical College Hospital  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Peking Union Medical College Hospital  Beijing People's Republic of China"},{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Peking Union Medical College and Chinese Academy of Medical Sciences  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingwei","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Peking Union Medical College Hospital  Beijing People's Republic of China"},{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Peking Union Medical College and Chinese Academy of Medical Sciences  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muyang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Peking Union Medical College Hospital  Beijing People's Republic of China"},{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Peking Union Medical College and Chinese Academy of Medical Sciences  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Peking Union Medical College Hospital  Beijing People's Republic of China"},{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Peking Union Medical College and Chinese Academy of Medical Sciences  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xisheng","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Peking Union Medical College Hospital  Beijing People's Republic of China"},{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Peking Union Medical College and Chinese Academy of Medical Sciences  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13018\u2010020\u201001707\u20105"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.2106\/jbjs.24.01060"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arth.2022.06.014"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arth.2022.03.003"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00402\u2010019\u201003127\u20105"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.24398"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics12051248"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s43019\u2010025\u201000263\u20108"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ksa.12696"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina60111757"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.2106\/jbjs.24.00984"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12891\u2010025\u201008585\u20100"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.blo.0000093002.90435.56"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13018\u2010023\u201003982\u20104"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arth.2017.04.032"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.3646"},{"key":"e_1_2_15_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11164796"},{"key":"e_1_2_15_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.622262"},{"issue":"2","key":"e_1_2_15_20_1","first-page":"655","article-title":"Metformin Induces the M2 Macrophage Polarization to Accelerate the Wound Healing via Regulating AMPK\/mTOR\/NLRP3 Inflammasome Singling Pathway","volume":"11","author":"Qing L.","year":"2019","journal-title":"American Journal of Translational Research"},{"key":"e_1_2_15_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.726490"},{"key":"e_1_2_15_22_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2025.3471"},{"key":"e_1_2_15_23_1","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.220952"},{"key":"e_1_2_15_24_1","doi-asserted-by":"publisher","DOI":"10.2106\/jbjs.20.01535"}],"container-title":["Orthopaedic 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