REVIEW article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1627691
Emerging Therapeutic Potential of Glucagon-Like Peptide-1 Receptor Agonists in Knee Osteoarthritis: A Systematic Review
Provisionally accepted
- 1Luoyang Orthopedic Traumatological Hospital, Luoyang, China
- 2Department of Geratology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- 3College of Orthopedics and Traumatology, Henan University of Traditional Chinese Medicine, Zhengzhou, China
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Abstract Objective: 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. Design: 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 December 31, 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. Findings: 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. Conclusion: These findings positioned GLP-1 RAs as promising disease-modifying agents for metabolic-associated KOA, particularly in obese or diabetic subpopulations.
Keywords: knee osteoarthritis, glucagon-like peptide-1 receptor agonists, Body Weight, glycemic control, Knee Pain
Received: 13 May 2025; Accepted: 23 Sep 2025.
Copyright: © 2025 Li, Yang, Li, Fu, Zhao, Wu, Guo and Yue. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jiayi Guo, doctorguojy@outlook.com
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.