[Glucagon-like peptide-1 receptor agonists: from metabolic regulation to rheumatic disease therapy]

Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RA), originally developed for type 2 diabetes mellitus and obesity, have attracted considerable attention in rheumatology due to their pleiotropic effects. Accumulating evidence indicates that GLP-1RA not only indirectly reduce inflammation through weight loss and metabolic improvement, but also directly act on GLP-1 receptors expressed on immune cells and musculoskeletal cells, exerting anti-inflammatory and tissue-protective effects independent of weight reduction. In recent years, several large real-world studies and randomized controlled trials have shown that GLP-1RA may improve disease activity and reduce cardiovascular events and mortality in osteoarthritis, rheumatoid arthritis (RA), psoriasis/psoriatic arthritis, and systemic lupus erythematosus (SLE). However, the available evidence has notable limitations: most studies are retrospective, with limited sample sizes; different GLP-1RA are often analyzed as a single class; the weight-loss effect is difficult to dissociate from direct anti-inflammatory action; and randomized controlled trials in non-obese, non-diabetic rheumatic patients are lacking. This review systematically summarizes the molecular mechanisms and clinical evidence of GLP-1RA in rheumatic diseases (including RA, psoriasis/psoriatic arthritis, osteoarthritis, and SLE), and based on this, the authors' perspective is put forward: currently, GLP-1RA should only be recommended for rheumatic patients with overweight/obesity or type 2 diabetes who also have high cardiovascular risk. Future research should prioritize head-to-head comparisons of different GLP-1RA, mechanistic studies independent of weight loss, and exploration of combination strategies. It is believed that GLP-1RA hold promise to usher in a new era of "metabolic-immune" synergistic intervention in rheumatology, but their benefits and risks must be carefully evaluated.