Obesity-driven Cardiovascular Risk: Role of GLP-1 Receptor Agonists and Dual GIP/GLP-1 Receptor Agonists

Obesity is now a major global public health concern and a recognised risk factor for Cardiovascular Disease (CVD), the leading cause of morbidity and mortality worldwide. Chronic lowgrade inflammation, oxidative stress, insulin resistance, dyslipidemia, and endothelial dysfunction are promoted by excessive adiposity, which in turn contributes to atherosclerosis and cardiovascular damage. Abnormal adipokine secretion with increased tumour necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1 and decreased adiponectin levels plays a major role in metabolic and vascular dysfunction. Furthermore, increased levels of retinol-binding protein-4 have been associated with insulin resistance and cardiometabolic impairment. As a result, weight loss is now considered a key therapeutic target for mitigating the cardiovascular risk associated with obesity. In recent times, incretin-based therapies, especially glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists, have provided significant cardiometabolic advantages. Both semaglutide and tirzepatide have demonstrated robust efficacy in the treatment of obesity, achieving approximately 15-20% body weight loss, along with beneficial effects on glycaemic control, lipid profile, systemic inflammation, and endothelial function. Incretin-based therapies are supported by cardiovascular benefits demonstrated in LEADER, SUSTAIN-6, and SELECT, which have shown significant reductions in Major Adverse Cardiovascular Events (MACE). More recent data also indicate additional antiinflammatory and endothelium-protective actions; however, many of the cardiovascular benefits may be attributable to weight loss and metabolic improvement. Tirzepatide has shown superior metabolic and weight-loss efficacy in various trials, but long-term cardiovascular outcome data, as well as specific head-to-head cardiovascular outcome trials, are limited. In addition, issues of long-term adherence, treatment costs, access, and maintenance of weight loss after treatment discontinuation need to be addressed. In summary, incretins and the incretin-based therapies currently available are promising strategies for reducing cardiovascular risk in obesity; further long-term comparative and real-world studies are needed to confirm their full cardiovascular potential.

Preparing paper insights from the available abstract and paper details.

Authors

Amandeep Kaur; Okesh Saini; Mohd Haneef; sourabh Kosey

Published

Sep 14, 2026

Journal or venue

Glucolipid Metabolic Disorders

DOI

10.2174/0129499011491956260906185203

Paper type

journal article

Source

Crossref