GLP-1 RECEPTOR AGONISTS IN OSTEOARTHRITIS: A STATE-OF-THE-ART REVIEW

N.G. Biavardi¹ , F. Pezone² , G. Placella¹ , M. Alessio-Mazzola² , M. Conca², V. Salini¹

¹ Vita-Salute University, IRCCS San Raffaele Hospital, Milan, Italy
² IRCCS San Raffaele Hospital, Milan, Italy

Correspondence to:

Journal of Orthopedics 2026 January-April; 18(1): 1-10
https://doi.org/10.69149/orthopedics/2026v18iss1_7

Received: 13 January 2026 Accepted: 16 February 2026

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Abstract

Osteoarthritis (OA) is a common degenerative joint disease with a complex pathophysiology involving mechanical stress, metabolic dysregulation, and chronic inflammation. Increasingly recognized as a metabolic disorder, OA has prompted interest in repurposing anti-diabetic medications, particularly glucagon-like peptide-1 receptor agonists (GLP-1RAs), for disease management. This review aims to critically evaluate the theoretical basis and emerging clinical evidence supporting the use of GLP-1RAs in OA treatment.  A comprehensive literature review was conducted, focusing on preclinical and clinical studies investigating the effects of GLP-1RAs on joint tissues, OA-related pathways, symptom modulation, and disease progression. GLP-1 receptors are expressed in joint tissues, where their activation influences key processes such as chondrocyte viability, extracellular matrix production, and inflammation suppression. Preclinical studies consistently demonstrate chondroprotective effects of GLP-1RAs, including reduced expression of matrix-degrading enzymes and inflammatory cytokines. Clinically, GLP-1RA therapy is associated with weight loss, a known modulator of OA symptoms. However, findings on direct symptom improvement and structural disease modification remain mixed. Some observational studies suggest a decreased need for knee surgery and slowed cartilage degradation, while others report a paradoxical increase in OA diagnoses among GLP-1RA users. The interaction between GLP-1RAs and OA pathophysiology is multifaceted and not yet fully understood. While preclinical data are promising, clinical evidence remains inconclusive. Robust, long-term randomized controlled trials are urgently needed to determine the disease-modifying potential of GLP-1RAs, identify responsive patient subgroups, and develop refined outcome measures to assess therapeutic efficacy in OA.

Keywords: chondroprotection, GLP-1 receptor agonist, inflammation, obesity, type 2 diabetes