Role of endogenous incretin hormones, GLP-1 and GIP in cardiovascular physiology

Jan 18, 2026Canadian journal of physiology and pharmacology

How natural incretin hormones GLP-1 and GIP influence heart and blood vessel function

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Abstract

Incretin hormones, particularly glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are critical regulators of glucose metabolism and cardiovascular health.

Endogenous GLP-1 enhances insulin secretion and promotes appetite suppression.
GLP-1 reduces inflammation and improves heart function during low blood flow conditions.
Endogenous GIP plays a role in insulin secretion and the formation of fat cells.
In obesity and type 2 diabetes, the secretion of incretins and their insulin-promoting effects are altered.
GLP-1 receptor agonists and dual GLP-1/GIP agonists may help manage metabolic dysfunction and prevent cardiovascular issues.

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Obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD) are closely related conditions contributing to the global rise in cardiometabolic disease. Incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have emerged as critical regulators of glucose metabolism, pancreatic function, and cardiovascular physiology. However, despite increasing clinical use of GLP-1 receptor agonists and dual GLP-1/GIP agonists, the precise mechanisms by which endogenous incretins influence cardiovascular tissues remain incompletely understood, particularly in the context of obesity and T2D. This review explores the history, signalling mechanisms, and physiological actions of natural endogenous GLP-1 and GIP, with a focus on cardiovascular physiology. Endogenous GLP-1 promotes insulin secretion, β-cell survival, and appetite suppression, and exerts protective effects on the endothelium. GLP-1 also reduces inflammation, enhances nitric oxide production, and improves myocardial glucose utilization during ischemia. Endogenous GIP is involved in insulin secretion, β-cell survival, and adipogenesis. In obesity and T2D, incretin secretion and insulinotropic effects are altered. The therapeutic potential of GLP-1 receptor agonists and emerging dual GLP-1/GIP agonists have been shown to aid in managing metabolic dysfunction and more recently in preventing cardiovascular complications.

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Role of endogenous incretin hormones, GLP-1 and GIP in cardiovascular physiology

Abstract

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