Effects of glucagon like peptide-1 receptor agonists and their combination with sodium-glucose cotransporter-2 inhibitors on myocardial deformation and work index in type 2 diabetes: 1 year follow up
Authors: Ikonomidis I , Pavlidis G , Thymis J , Birba D , Kalogeris A , Kousathana F , Kountouri A , Balampanis K , Parissis J , Andreadou I , Katogiannis K , Frogoudaki A , Vrettou AR , Iliodromitis EK , Lambadiari V 
Published: February 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.
Background/Introduction:
Type-2 diabetes mellitus (T2DM) exacerbates mechanisms of atherosclerosis and heart failure.

Purpose
We investigated the effect of novel antidiabetic drugs, glucagon like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and their combination on myocardial function.

Methods
A hundred-sixty T2DM patients (age: 58 ± 10years) were randomized to insulin (n = 40), liraglutide (n = 40), empagliflozin (n = 40) or their combination (GLP-1RA + SGLT-2i) (n = 40) as add-on to metformin. We measured at baseline and 1 year post-treatment: a) global LV longitudinal strain (GLS), systolic (GLSR) and diastolic (GLSR E) strain rate, global circumferential (GCS) and radial (GRS) strain, peak twisting (pTw), peak twisting velocity (pTwVel) and peak untwisting velocity (pUtwVel), b) global myocardial work index (GWI), global constructive (GCW) and global wasted work (GWW) derived by pressure-myocardial strain loops using speckle tracking imaging.

Results
After 1 year of treatment, all patients improved GLS, GCS, GRS and pUtwVel (p &lt; 0.05). GLP-1RA or GLP-1RA + SGLT-2i provided a greater increase of GLS (11.5% and 13% vs. 6.8% and 2.3%), GWI (12.7% and 17.4% vs. 3.1% and 2%), GCW (12.3% and 15% vs. 2.2% and 7.8%) and a greater reduction of GWW (38.7% and 41.6% vs. 13.5% and 4.9%) compared with insulin or SGLT-2i, despite a similar HbA1c reduction (p &lt; 0.05 for all comparisons) (Table). Patients under combined treatment with GLP-1RA + SGLT-2i achieved a 2-fold reduction of pTw and a 2-fold increase of pUtwVel than those under each one regimen or insulin (p &lt; 0.05). The dual therapy showed the greatest effect on measured myocardial markers in LVEF &lt; 55% (p &lt; 0.05).

Conclusions
One year treatment with GLP-1RA or combination of GLP-1RA and SGLT-2i resulted in a greater improvement of myocardial deformation and effective cardiac work than insulin or SGLT-2i treatment, independently of glycemic control in T2DM.
All patients (n = 160) Insulin (n = 40) GLP-1RA (n = 40) SGLT-2i (n = 40) GLP-1RA + SGLT-2i (n = 40) p-value GLS, % Baseline -16.4 ± 3.7 -16.4 ± 3.5 -16.2 ± 3.5 -17 ± 4 -16 ± 4 0.139 1 year -17.9 ± 3.9 -17.6 ± 4.2 -18.3 ± 3.5 -17.4 ± 3.4 -18.4 ± 4.7 0.003 GWI, mmHg% Baseline 1538 ± 430 1644 ± 416 1510 ± 403 1536 ± 535 1463 ± 362 0.116 1 year 1692 ± 412 1696 ± 377 1730 ± 318 1568 ± 456 1772 ± 499 0.006 pTw, deg Baseline 15.7 ± 6 16 ± 5.1 15.6 ± 5 15.2 ± 6 16.1 ± 8 0.910 1 year 14.6 ± 5.1 15.4 ± 5.4 14.4 ± 5.4 14.7 ± 4.6 14 ± 5 0.034 pUtwVel, deg/s Baseline -104 ± 42 -100 ± 44 -107 ± 41 -101 ± 28 -111 ± 54 0.550 1 year -116 ± 49 -107 ± 55 -114 ± 45 -108 ± 38 -134 ± 61 0.017 Table