Effects of sodium-glucose contrasporter-2 inhibitors and glucagon-like peptide-1 receptor agonists on vascular function and liver steatosis in diabetes

Abstract

Abstract Background/Introduction Patients with type-2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) present increase risk of cardiovascular disease. Sodium-glucose contrasporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have been shown to significantly reduce the risk of cardiovascular complications. Purpose The aim of the study was to investigate the effect of treatment with SGLT-2i or GLP-1RA on vascular function and liver steatosis and fibrosis in patients with T2DM and NAFLD. Methods Thirty patients with T2DM and NAFLD (mean age: 57±11 years) were randomized to receive SGLT-2i (dapagliflozin; n=15) or GLP-1RA (dulaglutide; n=15). At baseline and at 6 months post-treatment, we measured: (1) Perfused boundary region (PBR) of the sublingual microvessels with a diameter 5-25μm using Sidestream Dark Field camera (Microscan, Glycocheck). Increased PBR indicates reduced glycocalyx thickness. (2) Pulse wave velocity (PWV) and augmentation index (AI) using Complior (ALAM Medical), (3) NAFLD fibrosis score (NFS), and (4) Controlled attenuation parameter (CAP) score to assess steatosis grade and liver stiffness (E) to evaluate fibrosis score using liver elastography (FibroScan, Echosens). Results At baseline, patients between the two groups had similar age, sex, HbA1c, steatosis grade, fibrosis score and markers of vascular function (p>0.05). Compared with baseline, all patients had reduced PBR, PWV, AI, NFS, CAP and E (p<0.05) after 6-month treatment. In the whole study population, the percentage reduction of markers of steatosis (NFS) correlated with the corresponding decrease in PBR (r=0.34, p=0.040) and PWV (r=0.31, p=0.043) post-treatment. Both treatments with SGLT-2i and GLP-1RA reduced markers of liver steatosis and fibrosis (Table). Conclusion Both treatments with SGLT-2i and GLP-1RA improve vascular function and reduce liver steatosis in patients with T2DM and NAFLD after 6-month treatment.Table