Implications of Glucagon‐Like Peptide‐1 Signaling for Hemophilic Arthropathy, Joint Inflammation, and Cartilage Degeneration: A Narrative Review

Abstract

INTRODUCTION: Hemophilic arthropathy (HA) is a progressive, inflammatory joint disease that develops despite effective control of bleeding in people with hemophilia (PWH). Increasing evidence suggests that HA is initiated and then maintained by a complex cycle of synovial macrophage activation, angiogenesis, and cartilage catabolism-pathways shared with osteoarthritis (OA) and inflammatory arthritis. Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RA), initially developed for diabetes and obesity, have emerged as pleiotropic immunometabolic modulators with potent anti-inflammatory, chondroprotective, anti-angiogenic, and analgesic properties. METHODS: A narrative review was undertaken to examine the potential role of GLP-1RA in HA. RESULTS: Although GLP-1RA have not yet been studied directly in hemophilia, a large and growing preclinical and clinical literature in OA and inflammatory arthritis provides strong mechanistic justification for their relevance in HA. CONCLUSION: This review integrates experimental, translational, and epidemiologic data on GLP-1 signaling in joint biology and proposes a stage-specific framework for how GLP-1 pathways might modify HA downstream of bleeding, the initiating event.