Incretin-Based Therapies: A Paradigm Shift in Blood Pressure Management?

In the management of hypertension, only limited advances have been made over the past decades. Recent studies highlight the potential of next-generation incretin-based therapeutics, such as GLP-1 RAs (glucagon-like peptide-1 receptor agonists) like semaglutide and dual GLP-1/GIP (glucose-dependent insulinotropic polypeptide) receptor agonists like tirzepatide. These drugs not only promote weight loss but also substantially lower blood pressure (BP) and reduce cardiovascular end points. The extent to which incretin-based therapies improve disease outcomes via weight loss versus so-called direct tissue effects is the subject of great interest, not only for BP but also for other clinical outcomes. Although, incretin-based therapeutics were initially not designed to treat hypertension, clinical studies demonstrate an impressive reduction in BP in patients treated with these agents, with an even more pronounced effect in patients with obesity and hypertension. The current hypertension guidelines must address the robust evidence supporting the use of incretin-based therapeutics in patients with hypertension. A caveat is that no trial to date has used BP reduction as the primary end point when investigating the interaction between GLP-1 or GLP-1/GIP receptor agonists and antihypertensive medications. However, in patients with type 2 diabetes or a body mass index >27 kg/m², these drugs are widely used and lower BP. Taken together, incretin-based therapeutics represent a promising therapeutic tool to improve both BP and cardiovascular outcomes and help evolve the landscape of hypertension treatment.