Greater glucagon-like peptide-1 responses to oral glucose are associated with lower central and peripheral blood pressures

Abstract

Background and aim: Cardiovascular diseases (CVDs) are globally the leading cause of death and hypertension is a significant risk factor. Treatment with glucagon-like peptide-1 (GLP-1) receptor agonists has been associated with decreases in blood pressure and CVD risk. Our aim was to investigate the association between endogenous GLP-1 responses to oral glucose and peripheral and central haemodynamic measures in a population at risk of diabetes and CVD. Methods: This cross-sectional study included 837 Danish individuals from the ADDITION-PRO cohort (52% men, median (interquartile range) age 65.5 (59.8 to 70.7) years, BMI 26.1 (23.4 to 28.5) kg/m 2 , without antihypertensive treatment and known diabetes). All participants received an oral glucose tolerance test with measurements of GLP-1 at 0, 30 and 120 min. Aortic stiffness was assessed by pulse wave velocity (PWV). The associations between GLP-1 response and central and brachial blood pressure (BP) and PWV were assessed in linear regression models adjusting for age and sex. Results: A greater GLP-1 response was associated with lower central systolic and diastolic BP of − 1.17 mmHg (95% confidence interval (CI) − 2.07 to − 0.27 mmHg, P = 0.011) and − 0.74 mmHg (95% CI − 1.29 to − 0.18 mmHg, P = 0.009), respectively, as well as lower brachial systolic and diastolic BP of − 1.27 mmHg (95% CI − 2.20 to − 0.33 mmHg, P = 0.008) and − 1.00 (95% CI − 1.56 to − 0.44 mmHg, P = 0.001), respectively. PWV was not associated with GLP-1 release (P = 0.3). Individuals with the greatest quartile of GLP-1 response had clinically relevant lower BP measures compared to individuals with the lowest quartile of GLP-1 response (central systolic BP: − 4.94 (95% CI − 8.56 to − 1.31) mmHg, central diastolic BP: − 3.05 (95% CI − 5.29 to − 0.80) mmHg, brachial systolic BP: − 5.18 (95% CI − 8.94 to − 1.42) mmHg, and brachial diastolic BP: − 2.96 (95% CI − 5.26 to − 0.67) mmHg). Conclusion: Greater glucose-stimulated GLP-1 responses were associated with clinically relevant lower central and peripheral blood pressures, consistent with beneficial effects on the cardiovascular system and reduced risk of CVD and mortality.

Exposure–Response Analysis of Cardiovascular Outcome Trials With Incretin-Based Therapies

“…Moreover, a good fit was obtained between the observed relationship and the theoretically constructed model. The exposure-response relationship of GLP-1 was also demonstrated in a cross-sectional study, and linear regression analysis showed that higher glucose-stimulated GLP-1 levels were associated with clinically relevant lower blood pressure (associated with beneficial effects on the cardiovascular system) (35). In addition, a strong relationship was demonstrated between the mean and total drug exposure and MACE HR.…”

Impact of chronic GLP-1 RA and SGLT-2I therapy on in-hospital outcome of diabetic patients with acute myocardial infarction

“…In particular, Noyan-Ashraf et al [30] showed, in an experimental model, that liraglutide administration for 7 days before AMI induction reduces infarct size and improves survival by engaging pro-survival pathways in cardiomyocyte. Moreover, chronic treatment with GLP-1 RA has been shown to reduce blood pressure and plasma levels of atherogenic lipoproteins, potentially resulting in a better hemodynamic profile and in a lower coronary atherosclerotic burden when AMI occurs [31][32][33]. Similarly, SGLT-2i administration was found to preserve cardiac contractile function and efficiency during myocardial ischemia-reperfusion injury, and also to improve metabolism and up-regulation of antioxidative proteins after coronary artery ligation in animal models [34].…”

The right ventricular dysfunction and ventricular interdependence in patients with DM: assessment using cardiac MR feature tracking

“…The GLP-1R is a highly effective target for managing type 2 diabetes by increasing insulin secretion, which lowers blood glucose levels. Enhanced glucose-stimulated GLP-1 responses may have positive impacts on vascular function, reducing the risk of cardiovascular disease and mortality, and lowering central and peripheral blood pressure [ 22 ]. Diabetic patients face an increased risk of developing metabolic syndrome, and in some cases, thoracic adipose tissue secretes higher levels of Cer16:0, which amplifies oxidative stress, systemic inflammation and reduces endothelium-dependent vasodilation, resulting in adverse cardiac outcomes [ 23 ].…”