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.