Glucagon like peptide-1 receptor agonists and their combination with sodium-glucose cotransporter-2 inhibitors improve myocardial deformation and work index in type-2 diabetes after 12-month treatment

Abstract

Background/Introduction: Type‐2 diabetes mellitus (T2DM) exacerbates mechanisms of atherosclerosis and heart failure. Purpose: 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 LV myocardial function of T2DM patients. Methods: A hundred‐sixty T2DM patients (age: 58±10 years) 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, 4 and 12 months post‐treatment: a) global LV longitudinal strain (GLS), systolic (LongSr) and diastolic (LongSrE) strain rate, global circumferential (GCS) and radial (GRS) strain, peak twisting (pTw), peak twisting velocity (pTwVel) and peak untwisting velocity (pUtwVel), b) global myocardial global work index (GWI), global constructive (GCW) and global wasted myocardial work (GWW) derived by pressure‐myocardial strain loops using speckle tracking imaging. Results: At 4 and 12 months post‐treatment, all patients improved GLS, GCS, GRS and pUtwVel (p<0.05). At 12 months, GLP‐1RA or GLP‐ 1RA+SGLT‐2i provided a greater increase of GLS (11.5% and 13% vs. 6.8% and 2.3%), GCS (11.9% and 14.6% vs. 7.3% and 3.4%), GRS (3.8% and 4.3% vs. 2.2% and 1.6%), 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<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<0.05). The dual therapy showed the greatest effect on measured myocardial markers in patients with LVEF <55% (p<0.05). Conclusions: Twelve‐month treatment with GLP‐1RA or combination of GLP‐1RA and SGLT‐2i showed a greater improvement of myocardial deformation and effective cardiac work than insulin or SGLT‐2i treatment in T2DM. The combined therapy as second line was superior to either insulin, or GLP‐1RA and SGLT‐2i separately.