Glucagon-Like Peptide-1 (GLP-1) receptor agonists in rheumatology: A review of current evidence and future directions

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have improved the management of type 2 diabetes and obesity. Increasing evidence suggests their potential therapeutic role in rheumatic and musculoskeletal diseases, yet their precise mechanisms and clinical implications remain under investigation. This scoping review evaluates the current evidence on GLP-1 RAs in inflammatory arthritis, osteoarthritis, systemic autoimmune diseases, and other rheumatic conditions. This systematic literature search followed PRISMA-ScR guidelines and identified 52 studies and seven clinical trials from Scopus, PubMed, and ClinicalTrials.gov. Although most of the included studies had a risk of bias, the findings suggest that GLP-1 RAs may influence inflammatory pathways, oxidative stress, and immune regulation in conditions such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE), osteoarthritis (OA), and gout. In RA and PsA, GLP-1 RAs have demonstrated potential disease-modifying effects, reducing inflammatory cytokine expression and improving metabolic parameters; however, their clinical impact remains partially linked to weight loss. Studies on OA indicate chondroprotective and anti-inflammatory properties, yet their effect on disease progression remains inconclusive.

Additionally, GLP-1 RAs have been associated with cardiovascular and renal benefits in SLE, though concerns about autoimmune activation persist. Despite promising findings, several challenges remain, including heterogeneous clinical responses, the need for head-to-head comparisons with standard rheumatologic therapies, and a lack of long-term safety data in autoimmune conditions. Drug-induced autoimmune phenomena, cost considerations, and accessibility limitations must be addressed. Future research should focus on distinguishing between metabolic and direct immunomodulatory effects, optimizing combination therapies, and evaluating safety concerns. GLP-1 RAs hold potential as a novel therapeutic approach in rheumatology, but further well-designed randomized controlled trials are essential to establish their clinical role.