Glucagon-like peptide-1 receptor agonists modestly reduced blood pressure among patients with and without diabetes mellitus: A meta-analysis and meta-regression

ABSTRACT Background The cardiovascular benefits provided by glucagon-like peptide-1 receptor agonists (GLP-1RAs) extend beyond weight reduction and glycemic control. One possible mechanism may relate to blood pressure (BP) reduction. We aim to quantify the BP lowering effect by GLP1-RAs. Methods A comprehensive database search for placebo-controlled randomized controlled trials (RCTs) on GLP-1RA treatment was conducted until December 2023. Data extraction and quality assessment were carried out, employing a robust statistical analysis using a random effects model to determine outcomes with mean difference (MD) in millimeters mercury (mmHg) and 95% confidence intervals (CIs). The primary endpoint was the mean difference in systolic and diastolic BP. Subgroup analyses and meta-regression were done to account for covariates. Results Compared to placebo, GLP-1RAs modestly reduced SBP (semaglutide: MD −3.40, [95% CI −4.22 to −2.59, p<0.001], liraglutide: MD −2.61, [95% CI −3.48 to −1.74, p<0.001], dulaglutide: MD −1.46, [95% CI −2.20 to −0.72, p<0.001] and exenatide: MD −3.36, [95% CI - 3.63 to −3.10, p<0.001]). This benefit consistently increased with longer treatment duration. Established people with type 2 diabetes experienced less SBP lowering with semaglutide. DBP reduction was only significant in the exenatide group (MD −0.94, [95% CI −1.78 to −0.1], p=0.03). Among semaglutide cohorts, mean change in hemoglobin A1c and mean change in body mass index were directly associated with SBP reduction. Conclusion Patients on GLP-1RA experienced modest SBP lowering compared to placebo. Only exenatide reduced DBP. Further studies are needed to clarify the mechanisms and the clinical benefit of GLP-1RA effects in BP reduction.