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

Abstract

AimThe 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.MethodsA 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.ResultsCompared 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.ConclusionPatients 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.

Cardiovascular and renal outcomes of glucagon-like peptide 1 receptor agonists among patients with and without type 2 diabetes mellitus: A meta-analysis of randomized placebo-controlled trials

“…The odds reduction in MACE with GLP-1 RAs do not significantly differ between those with BMI<30 or BMI>30. The protective effect of GLP-1 can be due to its direct effect in GLP-1 receptors in the heart, independent of its ability to decrease body weight [ 32 ] and improve lipid metabolism which are acted upon by GLP-1 receptors in the brain and adipose tissues [ 33 ].…”

Getting the measure of the pressure: Optimal assessment of the effects of glucagon‐like peptide‐1 receptor agonists on blood pressure

“…GLP-1 receptor agonists also induce modest (2-4 beats/min) tachycardia, irrespective of the presence of hypertension. These effects of GLP-1 receptor agonists on blood pressure are supported by Rivera et al, 4 who performed a systematic review and meta-analysis of randomized controlled trials relating to the effects of four GLP-1 receptor agonists, semaglutide subcutaneously, exenatide once weekly, liraglutide and dulaglutide, on blood pressure in both type 2 diabetes and obesity without type 2 diabetes. 4 Not surprisingly, Rivera et al report marked inconsistencies in the design and duration of these studies; moreover, 31 of 63 related to liraglutide.…”

“…These effects of GLP-1 receptor agonists on blood pressure are supported by Rivera et al, 4 who performed a systematic review and meta-analysis of randomized controlled trials relating to the effects of four GLP-1 receptor agonists, semaglutide subcutaneously, exenatide once weekly, liraglutide and dulaglutide, on blood pressure in both type 2 diabetes and obesity without type 2 diabetes. 4 Not surprisingly, Rivera et al report marked inconsistencies in the design and duration of these studies; moreover, 31 of 63 related to liraglutide. While a previous analysis suggested that blood pressure reduction did not contribute to the cardiovascular benefits observed in LEADER, 1 this issue remains contentious.…”

“…Although some guidelines suggest that blood pressure monitoring should be undertaken following an overnight fast, there has generally been a lack of attention to the timing of blood pressure measurements in relation to meals. None of the studies reported by Rivera et al 4 evaluated the impact of GLP-1 receptor agonists on postprandial blood pressure.…”

Semaglutide and Nonarteritic Anterior Ischemic Optic Neuropathy

“…It has long been observed that tight glycemic control can worsen diabetic retinopathy in the short term in some; however, this is outweighed by the long-term systemic benefits . Of note, only a modest lowering of systolic blood pressure has been noted with GLP-1 RAs use …”