Cardioprotective mechanisms and effects of glucagon-like peptide-1 receptor agonists in autoimmune rheumatic diseases.
This review examines the cardioprotective potential of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in patients with autoimmune rheumatic diseases (ARDs), a population at elevated risk of premature cardiovascular death. The authors synthesize evidence from landmark randomized controlled trials in diabetes and obesity—where GLP-1RAs demonstrated cardiovascular, kidney, and metabolic benefits—alongside observational studies in ARD populations (including rheumatoid arthritis and systemic lupus erythematosus) that reported reductions in cardiovascular event risk comparable to those seen in broader populations. The review outlines proposed direct and indirect cardioprotective mechanisms: GLP-1RAs address type 2 diabetes and obesity as cardiovascular risk factors, reduce lipid levels by mitigating post-prandial hyperlipidemia, lower blood pressure via carotid body-mediated sympathetic suppression, and exhibit anti-atherogenic and anti-inflammatory properties observed in murine models. Anti-inflammatory effects are attributed to direct activation of GLP-1 receptors on gut intraepithelial lymphocytes and indirect modulation of myeloid cell inflammation through central neuronal GLP-1 receptor activation. The authors acknowledge remaining knowledge gaps and note that much mechanistic evidence derives from animal studies. Overall, they conclude existing evidence is supportive but not definitive for GLP-1RA cardioprotection in ARDs.
Why this grade: This is a narrative review synthesizing RCT, observational, animal, and mechanistic data; it does not generate primary human trial evidence itself.
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.
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