GLP-1 RECEPTOR AGONISTS (GLP-1RAs) may offer potential cardiovascular benefits for people with autoimmune rheumatic diseases (ARDs), according to emerging evidence. ARDs, which include rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, and axial spondyloarthritis, are characterised with chronic systemic inflammation that accelerates atherogenesis and substantially increases premature cardiovascular death.
Elevated Cardiovascular Risk In ARDs
Patients with ARDs face heightened CV risk due to multiple factors: persistent inflammation, frequent use of glucocorticoids and NSAIDs, and higher prevalence of cardiometabolic conditions such as obesity, type 2 diabetes, and hypertension. Non-pharmacological strategies like optimised nutrition and physical activity remain foundational, but new drug classes including GLP-1RAs and SGLT2 inhibitors are expanding treatment options.
Understanding GLP-1RAs and Cardiovascular Health
GLP-1RAs mimic native glucagon-like peptide-1, a hormone secreted by intestinal L cells in response to food, which stimulates insulin release and regulates glucose. These drugs act on GLP-1 receptors expressed throughout the body, producing pancreatic and extra-pancreatic benefits such as reduced blood glucose, appetite, blood pressure, serum lipids, and systemic inflammation. In addition to controlling obesity and type 2 diabetes, two key cardiovascular risk factors, GLP-1RAs may stabilise atherosclerotic plaques, mitigate post-prandial hyperlipidaemia, and reduce sympathetic nervous system activity that contributes to elevated blood pressure.
Observational Evidence for GLP-1RAs
Real-world data in ARDs, particularly rheumatoid arthritis and systemic lupus erythematosus, suggest GLP-1RA use is associated with lower rates of major adverse cardiovascular events and all-cause mortality, mirroring findings in broader populations. Mechanistic studies in mice show anti-inflammatory and anti-atherogenic effects, including direct attenuation of T-cell-mediated inflammation via gut receptors and indirect modulation of myeloid cell activity through central neuronal pathways. Early reports also indicate potential benefits in heart failure with preserved ejection fraction.
Remaining Questions and Future Directions
Despite promising findings, data for other ARDs remain limited. Future research should explore long-term safety, efficacy in combination with SGLT2 inhibitors, and the role of multi-agonist therapies targeting GIP, glucagon, or amylin pathways. Clarifying whether cardioprotective and anti-inflammatory effects occur independently of weight loss and glucose control will be critical for assessing clinical impact.
Clinical Implications
GLP-1RAs may represent a valuable option for clinicians managing patients with ARDs and concurrent cardiovascular-kidney-metabolic conditions. While more studies are needed, current evidence supports their potential to reduce CV risk through multiple direct and indirect mechanisms, offering hope for improved outcomes in a population with historically elevated premature mortality.
Reference
Karacabeyli D, Lacaille D. Cardioprotective mechanisms and effects of glucagon-like peptide-1 receptor agonists in autoimmune rheumatic diseases. Rheumatology (Oxford). 2026;DOI:10.1093/rheumatology/keag147.
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