Cardiovascular complications in Diabetes: The role of NLRP3 inflammasome and targeted interventions

Diabetes mellitus (DM) is a major risk factor for atherosclerotic cardiovascular disease (ASCVD), driven by complex metabolic and inflammatory pathways. Among these, the NLRP3 inflammasome has emerged as a crucial mediator linking hyperglycemia, oxidative stress, and chronic inflammation to vascular dysfunction. Dyslipidemia, endothelial dysfunction, and excessive reactive oxygen species (ROS) production further exacerbate plaque formation and cardiovascular complications. Recent cardiovascular outcome trials (CVOTs) highlight the cardioprotective benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), while novel anti-inflammatory strategies, including IL-1β inhibition and NLRP3-targeting agents, offer promising therapeutic avenues. This review explores the molecular mechanisms underlying diabetic atherosclerosis, with a unique emphasis on the role of the NLRP3 inflammasome in disease progression and how targeted interventions including SGLT2 inhibitors, GLP-1 receptor agonists, and emerging NLRP3-modulating agents can be integrated with precision medicine strategies. Unlike existing reviews, we highlight how genomic, epigenetic, and phenotypic stratification can guide combination therapies to optimize cardiovascular protection. Integrating individualized anti-inflammatory and metabolic interventions may provide tailored cardiovascular care, reducing morbidity and mortality in diabetic patients. Future research should focus on refining these personalized approaches to mitigate diabetes-associated cardiovascular complications.