Emerging therapeutic potential of glucagon-like Peptide-1 receptor agonists in knee osteoarthritis: a systematic review.

Abstract

<h4>Objective</h4>This study aims to systematically investigate the clinical efficacy and mechanisms of glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs) in the treatment of knee osteoarthritis (KOA), elucidate their underlying mechanisms, and propose potential future research directions.<h4>Design</h4>This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We reviewed literature from PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov up to 31 December 2024. The search strategy combined "GLP-1″ and "KOA". We included studies on GLP-1 RAs and KOA in humans and animals, excluding conference abstracts, reviews, letters, case reports, and other similar types of publications.<h4>Findings</h4>Fifteen studies were included, covering six clinical investigations and nine fundamental research studies. Clinical evidence showed GLP-1 RAs significantly improved pain scores and function while reducing KOA incidence. Mechanistic studies reveal multi-target effects, including: 1) Metabolic regulation, 2) Anti-inflammatory action, and 3) Cartilage preservation through autophagy activation and apoptosis inhibition. Safety analysis notes gastrointestinal and tumor events. At the same time, we are concerned about a declining trend in long-term compliance with GLP-1 RAs.<h4>Conclusion</h4>These findings positioned GLP-1 RAs as promising disease-modifying agents for metabolic-associated KOA, particularly in obese or diabetic subpopulations. While current evidence supports therapeutic potential, confirmatory phase III trials and long-term safety monitoring are needed to establish clinical guidelines.<h4>Systematic review</h4>https://www.crd.york.ac.uk/PROSPERO2/view/CRD420250656321, Identifier, CRD420250656321.