Twelve-month treatment with glucagon-like peptide-1 receptor agonists or sodium-glucose co-transporter-2 inhibitors improves arterial function and myocardial deformation after ischemic stroke

Background/Introduction Patients with type 2 diabetes mellitus (T2DM) and ischemic stroke present impaired markers of endothelial, vascular and left ventricular (LV) myocardial function. Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose contrasporter-2 inhibitors (SGLT-2i) are novel antidiabetic agents that appear to reduce the risk of cardiovascular complications. Purpose The aim of the study is to investigate the effect of treatment with GLP-1RA or SGLT-2i on endothelial glycocalyx, arterial stiffness and LV myocardial deformation in patients with T2DM and ischemic stroke. Methods We recruited in total 81 patients with T2DM and ischemic stroke who received dulaglutide (n=27), dapagliflozin (n=27) or insulin (n=27). We measured at baseline and at 12 months post-treatment the: a) perfused boundary region (PBR) of the sublingual arterial microvessels, as a marker of endothelial glycocalyx thickness, b) carotid-femoral pulse wave velocity (PWV-Complior; ALAM Medical), c) augmentation index (AIx), d) central systolic blood pressure (cSBP), and e) LV global longitudinal strain (GLS) using speckle-tracking echocardiography. Results At baseline, patients among the three groups had similar age, sex, HbA1c and markers of endothelial, vascular and LV myocardial function (p>0.05). Dulaglutide and dapagliflozin showed a greater reduction of PBR, PWV, AIx, central SBP, and GLS than insulin, despite a similar HbA1c reduction (p<0.05). After 12 months treatment, patients on dulaglutide and on dapagliflozin displayed a greater reduction of PBR (-10.7% and -8.6% vs. -1.8%), PWV (-11% and -14% vs. -3.7%), AΙx (-27.3% and -52% vs. -5.3%), cSBP (-3.6% and -5% vs. 0.9%), and a higher increase of GLS (14% and 9.6% vs. 3.6%) compared to patients on insulin (p<0.05 for all comparisons) (Table). In the patients who were treated with dulaglutide or dapagliflozin, the percentage reduction of PBR was correlated with the corresponding decrease of PWV (r=0.322, p=0.035) and with the increase of GLS (r=-0.348, p=0.029) after 12-month treatment. Conclusion Dulaglutide and dapagliflozin improve endothelial glycocalyx, vascular and LV myocardial deformation compared to insulin in patients with T2DM and ischemic stroke after 12 months treatment.