Cardiovascular disease remains a leading cause of mortality despite major advances in lipid lowering and risk-factor control, highlighting the importance of residual cardiovascular risk. Inflammation is a central driver of atherosclerosis, while obesity promotes chronic low-grade inflammation, adipose tissue dysfunction, ectopic fat accumulation, and vascular injury. This narrative review focuses on obesity-associated inflammation as an upstream contributor to residual atherosclerotic risk and evaluates whether incretin-based therapies modify this pathway through weight loss, metabolic improvement, and additional inflammatory or vascular mechanisms. Data from mechanistic studies, biomarker analyses, vascular imaging studies, and cardiovascular outcome trials are reviewed. Anti-inflammatory trials support inflammation as a modifiable therapeutic pathway, although clinical benefit depends on the therapeutic target, timing, and patient selection. Glucagon-like peptide-1 receptor agonists reduce inflammatory and oxidative stress biomarkers and show anti-atherosclerotic effects in experimental models, but human vascular imaging data remain inconclusive. Cardiovascular outcome trials establish benefit with several GLP-1 receptor agonists, including semaglutide in selected patients with overweight or obesity without diabetes. However, direct human evidence for receptor-mediated anti-inflammatory or anti-atherosclerotic effects remains limited, and the relative contributions of weight loss, metabolic improvement, and additional mechanisms remain uncertain.
Kafol et al. (Mon,) studied this question.