Glucagon-Like Peptide-1 Agonists and Blood Pressure Regulation: Molecular Mechanisms and Cardiovascular Implications.

Abstract

Incretin effect helps in regulating glucose homeostasis and maintaining glycaemic control within the human body. This effect is achieved by the two naturally occurring incretin hormones: glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Such hormones released by specialized entero-endocrine cells of the gastrointestinal tract cause insulin augmentation after food consumption. However, incretin effects are impaired in type 2 diabetic, primarily attributed to the deterioration of GLP-1 function along with decreased GLP-1 receptor expression. Targeting this hormone has, therefore, become an important therapeutic approach to treat this diabetic condition. Native GLP-1's brief half-life and rapid proteolytic degradation have generated significant enthusiasm in uncovering the long-acting GLP-1 receptor (GLP-1R) agonists to manage type 2 diabetes. These synthetic peptides mimic the natural GLP-1 to activate GLP-1R and effectively exert various physiological benefits in terms of weight management, blood pressure (BP), lipid profile, obesity and major adverse cardiovascular event. Although the BP-lowering effect of GLP-1R agonists is well documented in clinical trials, the underlying molecular mechanisms remain incompletely defined, since most evidence comes from animal and in vitro models rather than human studies. This gap limits translating the clinical benefit into targeted, mechanism-based practice. This review paper provides insights into the structure, function and expression of GLP-1 and its receptor. It also summarizes existing literature regarding different types of GLP-1R agonists, their effects on BP and how they exert their actions. Evidence indicates GLP-1R agonists produce a modest, consistent reduction in systolic blood pressure, heterogeneous across agents and confined to patients with elevated baseline BP, reflecting vascular, renal and anti-inflammatory mechanisms rather than a single pathway. Although animal models have contributed significantly to this area of study, the scarcity of human studies is noted, indicating a need for more investigation in this domain. Expanding research in humans will help in comprehending the impact of GLP-1R agonists on BP regulation and their underlying mechanisms.