Original Article Comparative effectiveness of glucagon-like peptide-1 receptor agonists versus dipeptidyl peptidase-4 inhibitors on noninvasive indices of hepatic steatosis and fibrosis in patients with type 2 diabetes mellitus Evangelia Makri a, * , Marina Kita b , Antonis Goulas a , Paraskevi Papaioannidou a , Zoe A. Efstathiadou b , Fotini Adamidou b , Stergios A. Polyzos a a First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece b Department of Endocrinology, Ippokration General Hospital, Thessaloniki, Greece article info Article history: Received 10 August 2020 Received in revised form 14 September 2020 Accepted 24 September 2020 Keywords: Dipeptidyl peptidase-4 inhibitor Fibrosis Glucagon-like peptide-1 receptor agonist Nonalcoholic fatty liver disease Type 2 diabetes mellitus abstract Background and aims: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in patients with type 2 diabetes mellitus (T2DM). There is currently no approved treatment for NAFLD. The main aim was the evaluation of the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RA) vs. dipeptidyl peptidase- 4 inhibitor (DPP-4i) treatment on noninvasive indices of hepatic steatosis and fibrosis in patients with T2DM. Methods: In this retrospective study, three noninvasive indices of hepatic steatosis [HSI, NAFLD ridge score, and triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) ratio] and five of fibrosis (APRI, FIB-4, NAFLD fibrosis score, BAAT and BARD) were calculated before and after (6e18 months) the addition of a DPP-4i (n ¼ 152) or a GLP-1 RA (n ¼ 37) in patients with T2DM. Results: Regarding steatosis indices, NAFLD ridge score was significantly decreased in the GLP-1 RA group (baseline: 0.90 ± 0.34, follow-up: 0.67 ± 0.24; p ¼ 0.001), but not in the DPP-4i group (p ¼ 0.25); the difference for group*time interaction was significant (p ¼ 0.02). HSI showed a trend between groups, being significantly different at baseline and follow-up (p < 0.001) with no significant difference in group*time interaction. Indices of fibrosis were not essentially changed within or between groups. Conclusions: NAFLD ridge score was significantly decreased after the addition of GLP-1 RA in patients with T2DM. This study warrants further prospective clinical trials. © 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved. 1. Introduction Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease, has an increasing prevalence and has been closely associated with obesity and type 2 diabetes mellitus (T2DM) [1]. NAFLD refers to a range of phenotypes, from nonalcoholic fatty liver (NAFL) or simple steatosis to nonalcoholic steatohepatitis (NASH) and NASH-related fibrosis, cirrhosis and hepatocellular carcinoma (HCC) [2]. Despite the effectiveness of lifestyle modifi- cations (diet and exercise) on improving NAFLD, those are difficult to achieve and sustain, underlying the need of pharmacological intervention [3]. Nonetheless, so far, there is no approved medi- cation for NAFLD treatment [4]. Furthermore, there is need for precise noninvasive diagnostic tools for NAFLD diagnosis, staging and follow-up, since liver biopsy, the current gold standard for Abbreviations: 1 H-MRS, proton magnetic resonance spectroscopy; ALT, alanine aminotransferase; ANCOVA, analysis of covariance; ANOVA, analysis of variance; APRI, AST to platelet ratio index; AST, aspartate aminotransferase; BAAT, BMI-Age- ALT-Triglycerides score; BARD, BMI-AST/ALT ratio-Diabetes score; BMI, body mass index; DPP-4i, dipeptidyl peptidase-4 inhibitor; FIB-4, fibrosis-4 index; GGT, gamma-glutamyl transferase; GLP-1 RA, glucagon-like peptide-1 receptor agonist; HbA1c, glycated hemoglobin; HCC, hepatocellular carcinoma; HDL-C, high-density lipoprotein cholesterol; HSI, hepatic steatosis index; LDL-C, low-density lipoprotein cholesterol; LFTs, liver function tests; MRI, magnetic resonance imaging; MRI-PDFF, magnetic resonance imagingeestimated proton density fat fraction; NAFL, nonal- coholic fatty liver; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; NFS, NAFLD fibrosis score; PLT, platelet; T2DM, type 2 diabetes mellitus; TG, triglycerides; US, ultrasound; WBC, white blood cells. * Corresponding author. MSc First Laboratory of Pharmacology, School of Medi- cine Campus of Aristotle University of Thessaloniki, Thessaloniki, Greece. E-mail address: evi-mak@hotmail.com (E. Makri). Contents lists available at ScienceDirect Diabetes & Metabolic Syndrome: Clinical Research & Reviews journal homepage: www.elsevier.com/locate/dsx https://doi.org/10.1016/j.dsx.2020.09.030 1871-4021/© 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved. Diabetes & Metabolic Syndrome: Clinical Research & Reviews 14 (2020) 1913e1919