Cardioprotective mechanisms and effects of glucagon-like peptide-1 receptor agonists in autoimmune rheumatic diseases

Cardiovascular diseases are the leading cause of premature death in many autoimmune rheumatic diseases (ARDs). Landmark randomized controlled trials in diabetes and obesity have demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RAs) have cardiovascular-kidney-metabolic benefits. Observational studies assessing GLP-1RAs in ARDs, including RA and SLE, have found reductions in risk of cardiovascular events similar to those reported in broader populations. GLP-1RAs likely exert their cardioprotective effects through direct and indirect mechanisms. GLP-1RAs treat type 2 diabetes and obesity, two important cardiovascular risk factors. They lower lipid levels by mitigating post-prandial hyperlipidaemia and reduce blood pressure by dampening carotid body-mediated sympathetic excitation. GLP-1RAs have anti-atherogenic and anti-inflammatory effects in mice. They attenuate T cell-mediated inflammation directly by activating GLP-1 receptors on gut intraepithelial lymphocytes, and myeloid cell-mediated inflammation indirectly by activating central neuronal GLP-1 receptors. While knowledge gaps remain, existing evidence supports a cardioprotective role for GLP-1RAs in ARDs.