Should Incretin Agonist-Based Brugs be Considered for First Line Antihypertensive Therapy?

This review evaluates the antihypertensive potential of next-generation incretin-based therapies, including GLP-1 receptor agonists and dual GLP-1/GIP receptor agonists. It examines their effects on blood pressure reduction, underlying mechanisms, clinical benefits, and implications for future guidelines.

Recent large-scale trials demonstrate that incretin-based therapies such as semaglutide and tirzepatide significantly reduce body weight, blood pressure, and cardiovascular outcomes. Mediation analyses indicate that weight loss explains a substantial proportion of blood pressure reduction, while direct effects on vascular function, renal sodium handling, and neurohumoral pathways also contribute. These effects are consistent across diverse populations, including individuals without overt hypertension. Incretin-based therapies represent a promising approach in hypertension management, combining metabolic and cardiovascular benefits. Despite the lack of trials with blood pressure as a primary endpoint, current evidence supports their use in selected high-risk populations and suggests an emerging role in future guideline recommendations.