Ambulatory blood pressure monitoring strengthens the cardiovascular signal of GLP-1RA: a meta-analysis of blood pressure and weight mediation

Abstract

Background: GLP-1 receptor agonists (GLP-1RA) and dual GLP-1/GIP agonists reduce cardiovascular events in patients with type 2 diabetes and obesity. The extent to which these benefits are mediated by blood pressure (BP) reduction vs. weight loss, especially in hypertensive patients, remains unclear.Methods: We conducted a systematic review and meta-analysis of randomized controlled trials published from January 2015 to April 2025 evaluating GLP-1RA or dual agonists. Eligible trials reported major adverse cardiovascular events (MACE) and changes in SBP and/or weight. Random-effects meta-analyses and meta-regressions were used to assess associations between MACE and reductions in BP or weight. Subgroup analyses were performed according to BP measurement method (clinical vs. ambulatory).Results: Twenty-one trials including 145 322 participants were analyzed. GLP-1RA significantly reduced MACE (pooled hazard ratio 0.86; 95% confidence interval 0.81-0.91). Meta-regression revealed that both SBP and weight reductions were independently associated with MACE risk reduction, with BP reduction showing a stronger relationship in trials using ambulatory BP monitoring.Conclusion: The cardiovascular benefits of GLP-1RA are likely influenced by both BP and weight reductions. Ambulatory BP monitoring strengthens the observed association between BP control and cardiovascular outcomes, although causality cannot be definitively established. These findings support the use of GLP-1RA in individuals with hypertension, including those with resistant phenotypes.