{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:56:50Z","timestamp":1781672210575,"version":"3.54.5"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Obesity is a major modifiable contributor to knee osteoarthritis (KOA), but excess adiposity has often been managed as a background risk factor rather than as a therapeutic target. In obesity-related KOA, adiposity may aggravate pain and disability through increased joint loading, low-grade inflammation, metabolic dysfunction, impaired physical activity, and reduced rehabilitation tolerance. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have created a new opportunity to achieve clinically meaningful weight loss in selected patients with obesity-related KOA. However, current evidence should be interpreted cautiously. Human data most strongly support weight-loss-mediated improvements in pain, function, and rehabilitation feasibility, whereas direct cartilage-, synovium-, subchondral bone-, or structure-modifying effects remain unproven. In this narrative review, we summarize the rationale, receptor biology, pharmacological mechanisms, inflammatory signaling hypotheses, clinical evidence, safety concerns, and implementation challenges related to GLP-1RA use in obesity-related KOA. We also position GLP-1RAs within a broader obesity-treatment continuum that includes lifestyle intervention, exercise-based rehabilitation, multidisciplinary weight management, other anti-obesity medications, bariatric surgery, symptom-bridging treatments, and arthroplasty when indicated. Particular attention is given to gastrointestinal intolerance, dehydration, gallbladder and pancreatitis-related concerns, lean-mass loss, perioperative management, treatment discontinuation, affordability, access, and long-term adherence. Overall, GLP-1RAs may become a useful component of integrated obesity-directed KOA care, but they should be regarded as part of a proposed framework rather than as validated disease-modifying therapy.<\/jats:p>","DOI":"10.3389\/fphar.2026.1856307","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:46:36Z","timestamp":1781671596000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["GLP-1 receptor agonists in obesity-related knee osteoarthritis: from weight loss to therapeutic pathway reconstruction"],"prefix":"10.3389","volume":"17","author":[{"given":"Jincan","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Massage Therapy, Xiamen Hospital of Traditional Chinese Medicine","place":["Xiamen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Massage Therapy, Xiamen Hospital of Traditional Chinese Medicine","place":["Xiamen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren","family":"Sa","sequence":"additional","affiliation":[{"name":"Department of Acupuncture, Sanya Hospital of Traditional Chinese Medicine","place":["Sanya, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongquan","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Massage Therapy, Xiamen Hospital of Traditional Chinese Medicine","place":["Xiamen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunqiong","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Massage Therapy, Xiamen Hospital of Traditional Chinese Medicine","place":["Xiamen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/s41584-020-00523-9","article-title":"Non-surgical management of knee osteoarthritis: comparison of ESCEO and OARSI 2019 guidelines","volume":"17","author":"Arden","year":"2021","journal-title":"Nat. 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