Incretins and the cardiovascular system: bridging digestion with metabolism.

The mechanisms driving the cardiovascular and renal benefits of therapies targeting intestinal hormones in type 2 diabetes are still not fully understood. We propose that incretin hormones-glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP)-act as a critical link connecting digestion, metabolism, and cardiovascular function, supporting physiological adaptations to nutrient intake. Incretin hormones help regulate blood flow and cardiac activity, enhancing nutrient absorption while protecting the heart and vessels. After meals, incretin hormones promote vasodilation-especially in the splanchnic and peripheral circulations-via nitric oxide, improving endothelial function, vascular flexibility, and blood pressure control, which supports tissue perfusion and meets the body's increased metabolic demands. GLP-1 also has mild inotropic effects, promoting efficient circulation without straining the heart. At the same time, vasodilation boosts glucose and lipid uptake, linking digestion directly to energy metabolism. These mechanisms lower vascular resistance, reduce cardiac workload, and improve myocardial glucose use, which becomes especially valuable during ischaemic events. Incretins also have anti-inflammatory and antioxidant effects, which help prevent endothelial dysfunction and arterial stiffening, reducing the risk of atherosclerosis. Clinically, GLP-1 receptor agonists and dual GLP-1 and GIP receptor agonists leverage these effects to improve cardiovascular and possibly renal outcomes in people with type 2 diabetes or obesity. By linking digestion, metabolism, and cardiovascular health, incretin-based therapies do more than just regulate blood sugar; they help reduce morbidity and mortality and are becoming a core component of modern diabetes care.