Effects of Glucagon‐Like Peptide‐1 Receptor Agonists, Sodium‐Glucose Cotransporter‐2 Inhibitors, and Their Combination on Endothelial Glycocalyx, Arterial Function, and Myocardial Work Index in Patients With Type 2 Diabetes Mellitus After 12‐Month Treatment

Abstract

Background We investigated the effects of insulin, glucagon‐like peptide‐1 receptor agonists ( GLP ‐1 RA ), sodium‐glucose cotransporter‐2 inhibitors ( SGLT ‐2i), and their combination on vascular and cardiac function of patients with type 2 diabetes mellitus. Methods and Results A total of 160 patients with type 2 diabetes mellitus were randomized to insulin (n=40), liraglutide (n=40), empagliflozin (n=40), or their combination ( GLP ‐1 RA + SGLT ‐2i) (n=40) as add‐on to metformin. We measured at baseline and 4 and 12 months posttreatment: (a) perfused boundary region of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness), (b) pulse wave velocity ( PWV ) and central systolic blood pressure, (c) global left ventricular longitudinal, circumferential, and radial strain, (d) myocardial work index (global work index) derived by pressure‐myocardial strain loops using speckle tracking imaging. Twelve months posttreatment, all patients improved perfused boundary region, PWV , global longitudinal strain, global circumferential strain, and global radial strain ( P <0.05). GLP ‐1 RA , SGLT ‐2i, and their combination showed a greater reduction of perfused boundary region, PWV, and central systolic blood pressure than insulin, despite a similar glycosylated hemoglobin reduction ( P <0.05). GLP ‐1 RA or GLP ‐1 RA + SGLT ‐2i provided a greater increase of global work index (12.7% and 17.4%) compared with insulin or SGLT ‐2i (3.1% and 2%). SGLT ‐2i or GLP ‐1 RA and SGLT ‐2i showed a greater decrease of PWV (10.1% and 13%) and central and brachial systolic blood pressure than insulin or GLP ‐1 RA ( PWV , 3.6% and 8.6%) ( P <0.05 for all comparisons). The dual therapy showed the greatest effect on measured markers in patients with left ventricular ejection fraction <55% ( P <0.05). Conclusions Twelve‐month treatment with GLP ‐1 RA , SGLT ‐2i, and their combination showed a greater improvement of vascular markers and effective cardiac work than insulin treatment in type 2 diabetes mellitus. The combined therapy as second line was superior to either ins...

Myocardial work in hypertensive patients with and without diabetes: An echocardiographic study

“…Our data showed that indices of myocardial work were deteriorated in hypertensive patients comparing with normotensive controls, but these parameters were even worse in hypertensive patients with concomitant DM. This is in line with recently published studies, 19‐23 but also adds some novelties such as concomitant effect of hypertension and diabetes on myocardial work. The present findings revealed that only constructive myocardial work was higher in patients with concomitant hypertension and DM comparing with those who had only hypertension.…”

Endothelial Dysfunction in Chronic Kidney Disease, from Biology to Clinical Outcomes: A 2020 Update

“…Newer antidiabetic agents, such as sodium-glucose cotransporter-2 (SGLT-2) inhibitors [219,220] and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) [221], decreased PWV in studies in patients with type-2 diabetes. Saxagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, prevented vascular remodeling and OS in a genetic model of diabetes [221].…”

Repurposing Antidiabetic Drugs for Cardiovascular Disease

“…All treatments led to reductions in HbA1c, total cholesterol, LDL cholesterol and triglycerides. The combination of empagliflozin and liraglutide was associated with the most favorable effects on myocardial functional markers (global longitudinal and radial strains, myocardial work index) and metabolic parameters (BMI, endothelial glycocalyx thickness, central systolic blood pressure) (Ikonomidis et al, 2020).…”

“…Treatment of obese, non-diabetic patients with exenatide and dapagliflozin for 52 weeks reduced bodyweight, total adipose tissue volume, LDL cholesterol, triglycerides, systolic blood pressure and the proportion of patients with pre-diabetes (Lundkvist et al, 2017). In a trial with T2D patients, the influence of liraglutide-empagliflozin combination therapy was compared to monotherapy with liraglutide, empagliflozin or insulin as add-on to metformin (Ikonomidis et al, 2020). All treatments led to reductions in HbA1c, total cholesterol, LDL cholesterol and triglycerides.…”