{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T23:51:42Z","timestamp":1792281102351,"version":"4.4.0"},"reference-count":19,"publisher":"BMJ","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Reg Anesth Pain Med"],"accepted":{"date-parts":[[2026,4,13]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Knee osteoarthritis (OA) is a leading cause of chronic pain and disability, with limited disease modifying therapies. While glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have established cardiometabolic benefits and have been associated with reductions in knee OA related pain, it is unclear whether they can reduce progression to total knee arthroplasty (TKA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective cohort study using the TriNetX Global Research Network, identifying adults with knee OA diagnosed between January 1, 2010, and December 31, 2024. Patients were stratified by GLP-1 RA exposure class (any GLP-1 RA or new generation agents, semaglutide or tirzepatide) and treatment duration (1 or 3 years), and then compared with propensity score matched non-exposed cohorts balanced for age, sex, race, musculoskeletal diagnoses, obesity related conditions, body mass index, and proxies for healthcare access. The primary outcome was cumulative incidence of TKA at 1, 3, 5, and 8 years. Hazard ratios (HRs) were estimated by Cox proportional hazards models and absolute risk differences from Kaplan\u2013Meier curves, expressed as exposed minus non-exposed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After propensity score matching, cohort sizes ranged from 13\u2009351 (new generation GLP-1 RA, 3\u2009year exposure) to 42\u2009062 patients (any GLP-1 RA, 1\u2009year exposure). GLP-1 RA use was associated with significantly lower cumulative TKA incidence across all exposure classes, durations, and follow-up intervals (all p&lt;0.001). With 1\u2009year exposure to any GLP-1 RA, the absolute risk difference at 8 years was \u22122.80\u2009percentage points (HR 0.90, 95%\u2009CI 0.83 to 0.98). Risk reductions were greater with new generation agents and longer duration: 3\u2009year exposure to semaglutide or tirzepatide gave an absolute risk difference of \u22124.71\u2009percentage points at 8 years (HR 0.72, 95%\u2009CI 0.67 to 0.78).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this large, multicenter, real world cohort study, GLP-1 RA use was associated with a significantly reduced long term risk of TKA in patients with knee OA, with effects that were greater with longer treatment duration and newer generation agents. These duration and agent dependent associations are consistent with potential disease modifying activity beyond weight loss alone, although prospective trials are needed to establish causality and define optimal treatment targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rapm-2026-107658","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:15Z","timestamp":1780444815000},"page":"rapm-2026-107658","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Glucagon-like peptide 1 receptor agonist use and risk of arthroplasty for knee osteoarthritis: retrospective database analysis"],"prefix":"10.1136","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6683-5033","authenticated-orcid":false,"given":"Victoria","family":"Carter","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA"},{"name":"Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7975-6905","authenticated-orcid":false,"given":"Ethan","family":"Desverreaux","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA"},{"name":"Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Idris","family":"Amin","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra E","family":"Fogarty","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, University of Utah School of Medicine, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0353-1002","authenticated-orcid":false,"given":"Nasir","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Ohio State University Wexner Medical Center, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4601-9837","authenticated-orcid":false,"given":"Ryan","family":"D\u2019Souza","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay","family":"Karri","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA"},{"name":"Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"2026060217001034000_rapm-2026-107658v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2016.136"},{"key":"2026060217001034000_rapm-2026-107658v1.2","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0090633","article-title":"The burden of musculoskeletal conditions","volume":"9","author":"Palazzo","year":"2014","journal-title":"PLoS 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