Background: Knee osteoarthritis (OA) is both a major and growing cause of disability and decreased quality of life but management remains limited to exercise, weight loss, symptomatic pain relief, and, potentially, knee arthroplasty. Numerous prescription drugs have been tested as disease-modifying osteoarthritis drugs (DMOAD). Among these, glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to reduce knee pain in patients with concurrent overweight and knee osteoarthritis (OA).[1,2] However, their effect on structural knee OA has yet to be demonstrated in a randomized, placebo-controlled clinical trial setting.

Objectives: To assess if treatment with a GLP-1RA could reduce the progression of structural knee OA. The primary objective was to compare the effect of weight loss and liraglutide, relative to weight loss and placebo, on structural knee OA change (measured as change in medial minimal JSW (mmJSW)) from baseline to week 60, in obese individuals with knee OA.

Methods: This secondary analysis followed a superiority framework of data from the LOSEIT trial, a randomised, parallel-group, placebo-controlled trial. The trial included adults from a secondary osteoarthritis outpatient clinic in Denmark aged 18 to 74 years with overweight (BMI ≥27 kg/m²), symptomatic and early-to-moderate radiographic knee OA, and maintaining stable body weight were eligible. Exclusion criteria included ongoing or recent participation in organised weight loss programs, current or recent use of weight loss medications, and end-stage radiographic knee OA. If successfully achieving at least a 5% weight loss (during an 8-week intensive dietary intervention (IDI) period) participants were randomised to receive either subcutaneously administered liraglutide 3 mg/day or identically appearing placebo throughout the 52-week main trial period (weeks 0 through 52; i.e., 60 weeks in total). Participants were randomised in a 1:1 manner in permuted blocks sized 2 to 6 to receive either 3 mg/day liraglutide or placebo. The randomisation process involved stratification based on sex (male vs. female), age group (<60 years vs. ≥60 years), and obesity class (BMI; <40 kg/m² vs. ≥40 kg/m²) status at trial enrolment (week -8). The primary outcome assessed in this study was the change in radiographic medial minimal joint space width (mmJSW). Analyses were conducted on the intention-to-treat population.

Results: From November 14, 2016, through September 12, 2017, 156 participants were randomly assigned to GLP-1RA (n = 80) or to placebo (n = 76). As reported in the primary analysis of the data, the GLP-1RA group lost more weight than the placebo group (mean difference, - 3.21 kg, 95% CI: - 6.39 to - 0.03; P = 0.050). The GLP-1RA group exhibited an increase in mean mmJSW of 0.22 mm (95% CI: 0.06 to 0.38) while the placebo group did not change (0.07 mm [95% CI: - 0.11 to 0.25]). However, the between-group comparison revealed no statistically significant difference in mean mmJSW (0.15 mm, 95% CI -0.06 to 0.36; P = 0.17).

Conclusion: While the results partially indicate a potentially favourable effect in the GLP-1RA group, the observed difference in structural knee OA changes on radiographs compared to placebo did not reach statistical significance. Further research should investigate whether treatment with more potent GLP-1 receptor agonists could lead to a more substantial improvement in structural knee OA.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: Mathias Willadsen Brejnebøl: None declared, Tobias Haugegaard: None declared, Robin Christensen: None declared, henrik gudbergsen: None declared, Henning Bliddal Consultant for the STEP-9 trial, Philip Hansen: None declared, Lars Erik Kristensen AbbVie, Amgen, Biogen Idec, Bristol-Myers Squibb, Celgene, Eli LIlly, Janssen Biotech, Merck & Co., Inc, Novartis, Pfizer, Sanofi: Has recieved fees for consultancy and speaking, Camilla Toft Nielsen: None declared, Cecilie Daugaard: None declared, Janus Nybing: None declared, Marius Henriksen serves on the advisory board of Thuasne, has received travel grants from Contura International A/S, Mikael Boesen: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.