The blood pressure lowering effects of glucagon-like peptide-1 receptor agonists: A mini-review of the potential mechanisms

Ribeiro-Silva, João Carlos; Tavares, Caio A M; Girardi, Adriana C. C.

doi:10.1016/j.coph.2023.102355

Cited by 12 publications

(4 citation statements)

References 67 publications

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“…Recent studies have found that the BP reduction seen with GLP-1 RAs is not related to blood glucose regulation [ 44 ]. Its antihypertensive mechanism may involve improving endothelial function, modulating smooth muscle cell phenotype, activating GLP-1R in the brainstem, weight loss, and natriuretic effects [ 44 , 45 ]. Chiriacò et al found that the dysregulation of BP circadian rhythm can increase subclinical organ damage and mortality [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

The effect of semaglutide on blood pressure in patients with type-2 diabetes: a systematic review and meta-analysis

Wu,

Tong,

et al. 2023

Endocrine

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Objective To evaluate the blood pressure (BP) lowering ability of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), in individuals with type-2 diabetes (T2D). Methods Randomized controlled trials (RCTs) comparing subcutaneous or oral semaglutide with placebo or other antihyperglycemic agents (AHAs) in T2D patients were identified by searching PubMed, Embase, Web of Science, ClinicalTrials.gov and Cochrane Library. These screened studies included the outcomes of interest: systolic and/or diastolic BP. Weighted mean differences (WMDs) and 95 % confidence intervals (CIs) were used to present the meta-analysis results. Pooled and sensitivity analyses were performed, and the risk of bias was evaluated. Results Twenty-nine RCTs with a total of 26985 participants were recruited in the final analysis. The WMD in change from baseline in systolic BP (SBP) of semaglutide versus placebo or other AHAs was −2.31 mmHg (95% CI: −3.11 to −1.51), while that for diastolic BP (DBP) was 0.09 mmHg (95% CI: −0.16 to 0.33). It also reduced glycated hemoglobin A1c (HbA1c) by 0.75% (95% CI: −0.92 to −0.58) and body weight loss by 2.80 kg (95% CI: −3.51 to −2.08). The reduction in SBP was similar for subcutaneous and oral administration of semaglutide, with −2.36 (95% CI: −3.38 to −1.35) and −2.50 (95% CI: −3.48 to −1.53), respectively. Conclusions In T2D, SBP decreased significantly in the semaglutide group compared with placebo or other active controls. According to the efficacy results from this meta-analysis, subcutaneous and oral semaglutide have similar SBP-reducing effects. Therefore, the treatment of T2D patients with subcutaneous semaglutide or oral preparations is beneficial for reducing SBP.

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Section: Discussionmentioning

confidence: 99%

The effect of semaglutide on blood pressure in patients with type-2 diabetes: a systematic review and meta-analysis

Wu,

Tong,

et al. 2023

Endocrine

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“…Several therapeutics developed to treat diabetes, such as sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists have demonstrated reductions in BP, which have generated much interest but are outside of the scope of this review. 25,26 While attempts to find large effect single variant pharmacogenomic markers for hypertension therapeutic efficacy have not been successful, a polygenic approach is more promising. This review will highlight the genetic architecture of key recent therapeutic targets in hypertension, review the existing evidence for pharmacogenomics (PGx) implementation in hypertension, and survey the potential for advanced modeling approaches to stratify therapeutic approaches based on polygenic risk score (PRS).…”

Section: Bp Genomicsmentioning

confidence: 99%

Use of Genomics to Develop Novel Therapeutics and Personalize Hypertension Therapy

Magavern,

Kapil,

Saxena

et al. 2024

ATVB

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Hypertension is a prevalent public health problem, contributing to >10 million deaths annually. Though multiple therapeutics exist, many patients suffer from treatment-resistant hypertension or try several medications before achieving blood pressure control. Genomic advances offer mechanistic understanding of blood pressure variability, therapeutic targets, therapeutic response, and promise a stratified approach to treatment of primary hypertension. Cyclic guanosine monophosphate augmentation, aldosterone synthase inhibitors, and angiotensinogen blockade with silencing RNA and antisense therapies are among the promising novel approaches. Pharmacogenomic studies have also been done to explore the genetic bases underpinning interindividual variability in response to existing therapeutics. A polygenic approach using risk scores is likely to be the next frontier in stratifying responses to existing therapeutics.

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“…8, 9 GLP-1 receptors are found in the hypothalamus and brainstem, the heart and vasculature, and the kidneys, suggesting multiple potential mechanisms that underlie the blood pressure-lowering effects of GLP1-RAs, independent of their effect on glycemic control. 10, 11 Among these include, but are not limited to, inhibition of sympathetic nerve excitation, reduction of vascular inflammation and arterial stiffness, and promotion of natriuresis and diuresis. 11 Previous studies have shown that GLP-1RAs reduce blood pressure by as much as 2-3 mmHg, with systolic BP being lowered more than diastolic BP.…”

Section: Introductionmentioning

confidence: 99%

“…10, 11 Among these include, but are not limited to, inhibition of sympathetic nerve excitation, reduction of vascular inflammation and arterial stiffness, and promotion of natriuresis and diuresis. 11 Previous studies have shown that GLP-1RAs reduce blood pressure by as much as 2-3 mmHg, with systolic BP being lowered more than diastolic BP. 12, 13 In subsequent meta-analyses, liraglutide and semaglutide have been demonstrated to provide a significant reduction in systolic blood pressure.…”

Section: Introductionmentioning

confidence: 99%

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

Rivera,

Lumbang,

Gaid

et al. 2024

Preprint

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BackgroundThe 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.MethodsA 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.ResultsCompared 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.ConclusionPatients 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.

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The blood pressure lowering effects of glucagon-like peptide-1 receptor agonists: A mini-review of the potential mechanisms

Cited by 12 publications

References 67 publications

The effect of semaglutide on blood pressure in patients with type-2 diabetes: a systematic review and meta-analysis

The effect of semaglutide on blood pressure in patients with type-2 diabetes: a systematic review and meta-analysis

Use of Genomics to Develop Novel Therapeutics and Personalize Hypertension Therapy

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

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