{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:51:02Z","timestamp":1792183862179,"version":"4.4.0"},"reference-count":25,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background: Knee osteoarthritis (KOA) in people with overweight or obesity is clinically heterogeneous, reflecting mechanical loading, synovial and systemic inflammation, metabolic dysfunction, structural severity, and pain-related factors. We evaluated multidomain outcomes after semaglutide initiation and characterized clinically relevant response patterns. Methods: This retrospective, self-controlled cohort included 93 adults treated in routine rheumatology care; 88 completed a six-month follow-up. There was no untreated concurrent comparator; within-patient changes and exposure\u2013outcome associations were therefore interpreted as non-causal. Changes in pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function, anthropometry, inflammatory markers, glycated hemoglobin (HbA1c), lipids, dose exposure, and safety were evaluated. Joint multivariable models included percentage weight loss and maximum achieved dose. Exploratory K-means phenotyping integrated dose, weight loss, body mass index (BMI) decrease, visual analog scale (VAS) and WOMAC improvement, and C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and HbA1c reductions, with candidate solutions and resampling stability examined. Results: At six months, mean weight decreased by 10.88 kg, VAS pain score by 2.47 points, WOMAC total by 22.50 points, CRP by 2.67 mg\/L, ESR by 7.62 mm\/h, and HbA1c by 0.51 percentage points (all p &lt; 0.001). Weight loss remained independently associated with WOMAC improvement, while achieved dose retained positive adjusted associations with pain, function, inflammatory, and metabolic changes. Exploratory clustering identified five clinically interpretable patterns along a broader response-intensity gradient, including high-burden multidomain response, high-dose concordant response, dose-modified intermediate response, inflammation-preserved response despite moderate weight loss, and dose-limited graded response. These observational coefficients and clusters cannot distinguish treatment-related effects from residual confounding or co-interventions. Conclusions: Substantial within-patient improvements were observed, but the uncontrolled design precludes causal attribution. The exploratory patterns may be compatible with contributions from baseline disease burden, dose exposure, mechanical unloading, and residual inflammatory variation; they do not establish weight-independent pharmacologic effects or validated patient subtypes. Prospective controlled, multicenter validation is required.<\/jats:p>","DOI":"10.3390\/jcm15155876","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T16:11:56Z","timestamp":1785168716000},"page":"5876","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Beyond the Scale: Changes in Pain, Physical Function (WOMAC), and Low-Grade Inflammation Following Semaglutide Treatment in Patients with Knee Osteoarthritis\u2014Results from a Six-Month Real-World Cohort"],"prefix":"10.3390","volume":"15","author":[{"given":"Alessandro","family":"Conforti","sequence":"first","affiliation":[{"name":"Rheumatology, ASL Roma 4, 00053 Civitavecchia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Lucchetti","sequence":"additional","affiliation":[{"name":"Rheumatology, ASL Roma 4, 00053 Civitavecchia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Ciampa","sequence":"additional","affiliation":[{"name":"Rheumatology, ASL Roma 4, 00053 Civitavecchia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Bonifacio","sequence":"additional","affiliation":[{"name":"Fisioterapia Medica srl, 00053 Civitavecchia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Giuseppe","family":"Musorrofiti","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Universit\u00e0 Telematica eCampus, 22060 Novedrate, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerio","family":"Cipolloni","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, A.O.U. \u201cVanvitelli\u201d University Hospital, \u201cLuigi Vanvitelli\u201d University, 80100 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Messina","sequence":"additional","affiliation":[{"name":"Rheumatology, ASL Roma 4, 00053 Civitavecchia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1016\/j.joca.2019.06.011","article-title":"OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis","volume":"27","author":"Bannuru","year":"2019","journal-title":"Osteoarthr. 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