Differential effects of glucagon-like peptide-1 receptor agonist classes on blood pressure: a systematic review and network meta-analysis of randomised controlled trials with meta-regression

Background and AimsRecent clinical trials have reported blood pressure (BP)-lowering effects of glucagon-like peptide-1 receptor agonists (GLP1Ra). A recent systematic review has focused on the effects of semaglutide. However, there has been no comprehensive evaluation of the BP effects of all GLP1Ra available, including the double agonist tirzepatide and the triple agonist retatrutide. Additionally, the extent to which BP reduction is mediated by weight loss remains unclear. This systematic review and network meta-analysis aimed to evaluate the impact of GLP1Ra on systolic and diastolic BP across randomized controlled trials (RCTs). MethodsPubMed/MEDLINE, Web of Science and Ovid/Embase were searched from their inception until 31st July 2024. RCTs involving adult patients treated with GLP1Ra that reported BP and weight changes were included. Pair-wise meta-analysis and meta-regression models were utilised. Network meta-analysis was conducted. Mean difference (MD) and its 95% confidence intervals (CIs) were reported. ResultsA total of 75 RCTs, including 114352 participants, were included. Retatrutide demonstrated the greatest reduction in systolic BP (MD: -7.0 mmHg; 95% CI: -10.5 to -3.5, followed by tirzepatide (MD: -5.2 mmHg; 95% CI: -6.9 to -3.5) and semaglutide (MD: -3.4 mmHg; 95% CI: -4.7 to -2.1). For diastolic BP, tirzepatide showed the largest reduction (MD: -1.7 mmHg; 95% CI: -2.6 to -0.8), followed by semaglutide (MD: -0.8 mmHg; 95% CI: -1.4 to -0.2). Mediation analysis indicated that weight loss partially mediated the BP-lowering effects of GLP1Ra. ConclusionRetatrutide, tirzepatide and semaglutide reduced systolic blood pressure compared to placebo. Tirzepatide and semaglutide also led to significant diastolic BP reductions. The triple agonist retatrutide emerged as the most effective agent for lowering systolic BP among all GLP1Ra classes.