Anti-inflammatory properties of GLP-1 receptor agonists and other ancillary benefits from a pharmacological perspective

Incretin-based therapies, particularly glucagon-like peptide-1 receptor agonists (GLP-1RAs), exert a wide range of beneficial effects beyond glycemic control, largely mediated by their anti-inflammatory properties. Chronic low-grade inflammation is a common pathological mechanism underlying metabolic, cardiovascular, hepatic, and neurodegenerative diseases. GLP-1RAs reduce systemic and tissue-specific inflammation through both direct and indirect mechanisms, including inhibition of nuclear factor kappa B signaling, reduction of proinflammatory cytokines, and modulation of immune cell activity, such as that of macrophages and microglia. In type 2 diabetes and obesity, GLP-1RAs improve insulin sensitivity and endothelial function by attenuating inflammation. In metabolic dysfunction-associated steatotic liver disease, GLP-1RAs reduce hepatic steatosis and fibrosis by modulating inflammation in hepatocytes and Kupffer cells. In cardiovascular disease, they mitigate atherosclerosis progression and improve vascular health. GLP-1RAs also exert direct nephroprotective effects by reducing renal inflammation, oxidative stress, and glomerular hyperfiltration in both diabetic and nondiabetic models. GLP-RAs have been also associated with the preservation of cognitive and motor function. Preclinical studies suggest that these neuroprotective effects may involve the attenuation of neuroinflammation and reduced aggregation of pathological proteins. Overall, these pleiotropic actions position incretin-based therapies as promising tools for the management of complex chronic diseases with an inflammatory component.