P2522The combined treatment with glucagon like peptide-1 analogues and sodium-glucose co-transporter 2 causes a greater improvement of arterial stiffness than each treatment alone in type 2 diabetes

Abstract

Introduction: Glucagon like peptide-1 analogues (GLP-1A) and sodium-glucose co-transporter 2 (SGLT2) are used in the treatment of type 2 diabetes mellitus (T2DM) and related with reduced cardiac events. We investigated whether a 3- month combined treatment with GLP-1A and SGLT2 causes a greater improvement of arterial stiffness than each treatment alone. Methods: Eighty patients with type 2 diabetes were randomized to receive the insulin +/- metformin (n=20), GLP-1A, liraglutide (n=20), the SGLT-2, empagliflozin (n=20) or their combination (GLP-1R+SGLT-2) for 3 months (n=20).We measured at baseline and after 3-months of treatment a) carotid-femoral pulse wave velocity (PWV - Complior SP), central systolic blood pressure (cSBP) and augmentation index (AI) (Arteriograph) b) the perfusion boundary region (PBR-micrometers) of the sublingual arterial microvessels, as a marker of endothelial glycocalyx thickness. Results: All four treatment groups had similar PBR, PWV, Aix, central SBP, brachial systolic SBP, glucose levels and HbA1 at inclusion (p>0.05 for between groups comparisons). After 3-month treatment, patients who received GLP-1R, SGLT-2 and their combination achieved a significant reduction of PBR, PWV, Aix, central SBP (p<0.05) while those who received insulin/metformin did not, despite a similar reduction of HbA1 in all treatment groups (p<0.05). Additionally, patients who were treated with the combination of GLP-1A and SGLT-2 showed a greater improvement of vascular markers than each treatment alone or treatment with insulin/metformin (table, p<0.05). After treatment, the reduction of PBR, suggesting improvement of glycocalyx thickness, was related with the changes in central SBP (r=0.40), Aix (r=0.45) and PWV (r=0.35) (p<0.05 for all correlations). Conclusion: Three-month treatment with a combination of GLP-1A and SGLT-2 showed a greater improvement of vascular markers than each treatment alone and insulin treatment in type 2 diabetes.