AIM: The cardiovascular benefits provided by glucagon-like peptide-1 receptor agonists (GLP-1RAs) extend beyond weight reduction and glycaemic control. One possible mechanism may relate to blood pressure (BP) reduction. We aim to quantify the BP-lowering effects of GLP1-RAs.
METHODS: A comprehensive database search for placebo-controlled randomized controlled trials 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 a mean difference (MD) in mmHg and 95% confidence intervals (CIs). The primary endpoint was the mean difference in systolic BP (SBP) and diastolic BP. Subgroup analyses and meta-regressions were done to account for covariates.
RESULTS: Compared with placebo, GLP-1RAs modestly reduced SBP [semaglutide: MD -3.40 (95% CI -4.22 to -2.59, p < .001); liraglutide: MD -2.61 (95% CI -3.48 to -1.74, p < .001); dulaglutide: MD -1.46 (95% CI -2.20 to -0.72, p < .001); and exenatide: MD -3.36 (95% CI -3.63 to -3.10, p < .001)]. This benefit consistently increased with longer treatment durations. Diastolic BP reduction was only significant in the exenatide group [MD -0.94 (95% CI -1.78 to -0.1), p = .03]. Among semaglutide cohorts, mean changes in glycated haemoglobin and mean changes in body mass index were directly associated with SBP reduction.
CONCLUSION: Patients on GLP-1RA experienced modest SBP lowering compared with placebo. This observed effect was associated with weight/body mass index reduction and better glycaemic control, which suggests that BP-lowering is an indirect effect of GLP-1RA and unlikely to be responsible for the benefits.
| Discipline Area | Score |
|---|---|
| Physician |  |
Physician rater
BP reduction is modest and tested to weight loss.
Physician rater
The effect on BP is indeed "modest." I think most of us would have expected this on the basis of weight reduction and improvement in glycemic control. It's not world-changing, but definitely good to know and have formally examined. The analysis is sound, but individual patient data are sorely needed. For example, to resolve issues like the higher degree of SBP reduction with lower baseline SBP, which is the opposite of what I would expect (and the opposite of what was seen with finerenone, for example), and may be due to the small number of trials. I note that the "central figure" concludes that GLP-1RA lowers SBP independent of glycemic control - this does not match the Conclusion in the abstract. Also, the independence of SBP lowering from glycemic control is not established, as far as I can see, in the Results; however, in the Discussion, the authors highlight a previous study that shows this using a form of mediation analysis.
, McMaster University