Effect of glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors and their combination on left atrial strain and arterial function

Abstract

Background: We investigated the effects of insulin, glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and their combination on left atrial function of patients with type 2 diabetes mellitus and we searched for a relation with arterial function Patients and methods: A total of 201 patients (59,5±9,1 year old, 161 male) with type 2 diabetes mellitus treated with metformin were randomized to insulin (n= 50 served as controls), liraglutide (n=51), empagliflozin (n=50) or their combination (GLP-1RA+SGLT- 2i) (n= 50) as add-on. We measured at baseline and 6 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 strain, (d) left atrial strain Results: Six months after intervention, all patients improved left atrial reservoir strain (GLP1RA 30,7±9,3 vs 33,9±9,7%, p = 0,011/SGLT2i 30 ±8,3 vs 32,3±7,3%, p = 0,04/ GLP1&SGLT2i 29,1±8,7 vs 31,3±8,2, p = 0,007) in comparison with controls (33±8,3% vs 32,8±7,4, p = 0,829) Also, patients treated with GLP1RA and their combination improved left atrial conduction strain (p<0.05). GLP-1RA or GLP-1RA+SGLT-2i provided a greater improvement in GLS compared with insulin or SGLT-2i (controls -18,5±3,9% vs - 19,1±3%, p = 0,202/GLP1RA -18,2 ±4,1% vs -19,1±3,5%, p = 0,03/SGLT2i -19±4,1% vs - 19,1±3,8%, p = 0,764/GLP1&SGLT2i -16,7±3,9% vs -17,5±4,3%, p = 0,026) SGLT-2i or GLP-1RA and SGLT-2i showed a greater decrease of PWV (Controls 12,06±3,02 vs 11,62±2,79 m/sec, p = 0,142/ GLP1 11,54 ±2,91 vs 11,45±2,52 m/sec, p = 0,822/ SGLT2 11,86±2,51 vs 11,33±2,28 m/sec, p = 0,047/ GLP1&SGLT2 12,01±2,46 vs 10,85±1,79 m/sec p = 0,021) and central and brachial systolic blood pressure than insulin or GLP-1RA. At baseline, there was a correlation of LA reservoir strain with PWV (r =-0,209, p = 0,008), central SBP (r =-0,151, p = 0,030), EF (r=0,214, p = 0,004), GLS (r =-0,279, p = 0,009). At 6 months follow up, there was a correlation of LA reservoir strain with PWV (r=0,217, p = 0,003), central SBP (r =0,214, p = 0,004), EF (r=-0,221, p = 0,049) GLS (r =0,275, p = 0,014) Conclusions: Treatment with GLP-1RA, SGLT-2i, and their combination for 6 months showed a greater improvement of left atrial function compared to insulin treatment in parallel with improvement arterial and myocardial function.