Four-month treatment with long-acting glucagon-like peptide-1 receptor agonists (GLP-1) or sodium-glucose co-trasporter-2 inhibitors (SGLT-2i) improves vascular function in type 2 diabetes mellitus

Abstract Background/Introduction Patients with type 2 diabetes mellitus (T2DM) and ischemic stroke present impaired markers of vascular and endothelial function. Glucagon-like peptide-1 receptor agonists (GLP-1) and sodium-glucose contrasporter-2 inhibitors (SGLT-2) are novel antidiabetic agents reducing the risk of cardiovascular complications. Purpose The aim of the study is to investigate the effect of treatment with GLP-1 or SGLT2 on arterial stiffness and endothelial glycocalyx 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 four months post-treatment the: a) Carotid-femoral pulse wave velocity (PWV-Complior; ALAM Medical), b) Augmentation index (Aix), c) Central systolic blood pressure (cSBP), and d) Perfused boundary region (PBR) of the sublingual arterial microvessels(marker of endothelial glycocalyx thickness), e) Left ventricular 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 and cardiovascular function (p>0.05). Dapagliflozin and dulaglutide showed a greater reduction of PBR, PWV and central SBP than insulin, despite a similar HbA1c reduction (p<0.05). After four months treatment, patients on dapagliflozin and on dulaglutide displayed a greater reduction of PWV (−10% and −8% vs −1%), of cSBP (−9% and −8% vs +1%), of Aix (−65% and −13% vs −3%) and of GLS (+11% and +7% vs +5%) compared to patients on insulin (p<0.05 for all comparisons) (Table 1). PBR values were improved only in patients who received dulaglutide (−4% vs dapagliflozin: −2% vs insulin +1%). Conclusions Dulaglutide and dapagliflozin improve cardiovascular function, but only dulaglutide improves endothelial glycocalyx in patients with T2DM and ischemic stroke after four months treatment. Funding Acknowledgement Type of funding sources: None.