Ambulatory BP and Weight Reduction as Predictors of GLP-1RA CV Benefit

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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 versus 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 systolic BP 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 HR 0.86; 95% CI 0.81–0.91). Meta-regression revealed that both systolic BP and weight reductions were independently associated with MACE risk reduction, with BP reduction showing a stronger relationship in trials using ambulatory BP monitoring.

Conclusions

The cardiovascular benefits of GLP-1RA are mediated by both BP and weight reductions. Ambulatory BP monitoring strengthens the observed association between BP control and cardiovascular outcomes. These findings support the use of GLP-1RA in individuals with hypertension, including those with resistant phenotypes.

Funding No external funding was received for this study.

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