Impact of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists on myocardial work and coronary flow in liver steatosis and diabetes

Abstract Background Individuals with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) have a higher likelihood of developing cardiovascular disease. Research indicates that sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) can substantially reduce the risk of cardiovascular complications. Purpose This study aimed to evaluate the impact of treatment with SGLT-2 inhibitors or GLP-1 receptor agonists on cardiovascular function, as well as liver steatosis and fibrosis, in individuals with T2DM and NAFLD. Methods Fifty patients with T2DM and NAFLD (average age: 56 ± 9 years) were randomly assigned to receive either SGLT-2i (dapagliflozin; n = 25) or GLP-1RA (dulaglutide; n = 25). Assessments were conducted at baseline, as well as after 6 and 12 months of treatment, and included: (1) perfused boundary region (PBR) of sublingual microvessels (5-25μm in diameter) using a dedicated camera, where an increased PBR signifies reduced glycocalyx thickness; (2) pulse wave velocity (PWV) measured with dedicated device; (3) coronary flow reserve (CFR) evaluated via Doppler echocardiography; (4) left ventricular global longitudinal strain (GLS) assessed through speckle-tracking echocardiography; (5) myocardial global work index (GWI), global constructive work (GCW), global wasted work (GWW) and myocardial global work efficiency (GWE), by longitudinal strain-peripheral blood pressure loops, (6) controlled attenuation parameter (CAP) score to determine the degree of liver steatosis and liver stiffness (E) to assess fibrosis severity; and (7) NAFLD fibrosis score (NFS). Results At baseline, patients between the two groups had similar age, sex, HbA1c, steatosis grade, fibrosis score and markers of cardiovascular function (p > 0.05). Compared with baseline, all patients had reduced PBR, PWV, CAP, E and NFS, GWW and increased CFR, GLS, GWI, GCW, GWE (p < 0.01) after 12-month treatment. In the whole study population, the percentage reduction of CAP and NFS was correlated with the corresponding decrease of PBR (r = 0.248 and r = 0.387), PWV (r = 0.290 and r = 0.281), GWW (r=0.325 and r=0.376) and with the increase of GLS (r = -0.320 and r = -0.295) after 12-month treatment (p < 0.05 for all correlations). Both treatments with SGLT-2i and GLP-1RA reduced markers of liver steatosis and fibrosis (Table). Conclusion Treatment with both SGLT-2i and GLP-1RA enhances cardiovascular function and decreases liver steatosis in patients with T2DM and NAFLD after 12 months.