Abstract
BackgroundIncretin-based therapies are used in the treatment of type 2 diabetes mellitus (T2DM) and obesity. We investigated the changes in arterial stiffness and left ventricular (LV) myocardial deformation after 6-month treatment with the GLP-1 analogue liraglutide in subjects with newly diagnosed T2DM.MethodsWe randomized 60 patients with newly diagnosed and treatment-naive T2DM to receive either liraglutide (n = 30) or metformin (n = 30) for 6 months. We measured at baseline and after 6-month treatment: (a) carotid-femoral pulse wave velocity (PWV) (b) LV longitudinal strain (GLS), and strain rate (GLSR), peak twisting (pTw), peak twisting velocity (pTwVel) and peak untwisting velocity (pUtwVel) using speckle tracking echocardiography. LV untwisting was calculated as the percentage difference between peak twisting and untwisting at MVO (%dpTw–UtwMVO), at peak (%dpTw–UtwPEF) and end of early LV diastolic filling (%dpTw–UtwEDF) (c) Flow mediated dilatation (FMD) of the brachial artery and percentage difference of FMD (FMD%) (d) malondialdehyde (MDA), protein carbonyls (PCs) and NT-proBNP.ResultsAfter 6-months treatment, subjects that received liraglutide presented with a reduced PWV (11.8 ± 2.5 vs. 10.3 ± 3.3 m/s), MDA (0.92 [0.45–2.45] vs. 0.68 [0.43–2.08] nM/L) and NT-proBNP (p < 0.05) in parallel with an increase in GLS (− 15.4 ± 3 vs. − 16.6 ± 2.7), GLSR (0.77 ± 0.2 vs. 0.89 ± 0.2), pUtwVel (− 97 ± 49 vs. − 112 ± 52°, p < 0.05), %dpTw–UtwMVO (31 ± 10 vs. 40 ± 14), %dpTw–UtwPEF (43 ± 19 vs. 53 ± 22) and FMD% (8.9 ± 3 vs. 13.2 ± 6, p < 0.01). There were no statistically significant differences of the measured markers in subjects that received metformin except for an improvement in FMD. In all subjects, PCs levels at baseline were negatively related to the difference of GLS (r = − 0.53) post-treatment and the difference of MDA was associated with the difference of PWV (r = 0.52) (p < 0.05 for all associations) after 6-month treatment.ConclusionsSix-month treatment with liraglutide improves arterial stiffness, LV myocardial strain, LV twisting and untwisting and NT-proBNP by reducing oxidative stress in subjects with newly diagnosed T2DM.ClinicalTrials.gov Identifier NCT03010683
Highlights
Incretin-based therapies are used in the treatment of type 2 diabetes mellitus (T2DM) and obesity
Changes in metabolic parameters and vascular markers after 6‐month treatment Treatment with liraglutide resulted in a greater weight loss, reduction in body mass index (BMI), waist circumference, and HbA1c in comparison to metformin (p < 0.05, Table 2)
Treatment with liraglutide caused a significant reduction in pulse wave velocity (PWV), augmentation index (AI), systolic blood pressure and central systolic blood pressure (p < 0.05, Tables 2 and 3) while these changes were not evident in patients treated with metformin (p > 0.05) after adjusting for HbA1c, weight, BMI and waist circumference
Summary
Incretin-based therapies are used in the treatment of type 2 diabetes mellitus (T2DM) and obesity. Type-2 diabetes mellitus (T2DM) is associated with cardiac dysfunction [1]. GLP-1 analogues are a class of antidiabetic medications that mimic the actions of the endogenous incretin GLP-1 through supraphysiological blood concentrations that are resistant to degradation by DPP-4. These drugs lower glucose levels by inhibiting the secretion of glucagon, by promoting the release of insulin in a glucose-dependent manner, by slowing gastric emptying, and by acting at the hypothalamus causing an anorexigenic effect and regulating energy balance [4]. Recent large scale study has demonstrated that in addition to improving glycaemic control and promoting weight loss, GLP-1 analogues may improve cardiovascular outcomes in patients at high cardiovascular risk [5]
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