Glucagon-like peptide and its receptor agonists for the treatment of rheumatic diseases

Table 1 Summary of glucagon-like peptide-1 and its receptor agonist(s) benefits across rheumatic diseases

Disease	Pathophysiology	Mechanism of action of GLP-1RAs	Key outcomes	Evidence type
OA	Cartilage degradation, synovial inflammation, obesity-related inflammation	↓ MMPs and TNF-mediated catabolic enzymes. ↓ Synovial inflammation. Weight reduction	Delayed cartilage degradation. Improved joint integrity. Reduced pain and stiffness	Preclinical (in vitro/animal)
RA	Autoimmune synovial inflammation, joint erosion	↓ NF-κB signaling. ↓ Pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). ↑ Treg activity	Reduced synovial inflammation. Reduced bone erosion. Improved immune regulation	Preclinical, limited clinical evidence
PsA	Inflammatory arthritis with metabolic syndrome involvement	↓ Th17/Th1 inflammatory pathways. ↓ Pro-inflammatory cytokines. Metabolic improvements (weight loss)	Decreased systemic inflammation. Potential joint protection. Improved metabolic comorbidities	Preclinical, limited clinical data
SLE	Autoantibody production, systemic inflammation	↓ Autoantibody production. ↓ Oxidative stress. Improved endothelial function	Reduced disease activity. Improved vascular outcomes	Preclinical (animal models), limited clinical
Common mechanisms	Chronic inflammation, metabolic dysregulation	↓ NF-κB signaling. ↑ cAMP leading to anti-inflammatory downstream effects. M2 macrophage polarization. Weight reduction	Reduced inflammatory burden. Improved metabolic profile	Preclinical and clinical (metabolic studies)

cAMP: Cyclic adenosine monophosphate; GLP-1RA: Glucagon-like peptide-1 and its receptor agonist(s); IL: Interleukin; MMP: Matrix metallopeptidase; NF-κB: Nuclear factor kappa B; OA: Osteoarthritis; PsA: Psoriatic arthritis; RA: Rheumatoid arthritis; SLE: Systemic lupus erythematosus; Th: T helper type; TNF-α: Tumor necrosis factor alpha.