Observational Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 14, 2022; 28(26): 3243-3257
Published online Jul 14, 2022. doi: 10.3748/wjg.v28.i26.3243
Impact of sodium glucose cotransporter-2 inhibitors on liver steatosis/fibrosis/inflammation and redox balance in non-alcoholic fatty liver disease
Francesco Bellanti, Aurelio Lo Buglio, Michał Dobrakowski, Aleksandra Kasperczyk, Sławomir Kasperczyk, Palok Aich, Shivaram P Singh, Gaetano Serviddio, Gianluigi Vendemiale
Francesco Bellanti, Aurelio Lo Buglio, Gaetano Serviddio, Gianluigi Vendemiale, Department of Medical and Surgical Sciences, University of Foggia, Foggia 71122, Italy
Michał Dobrakowski, Aleksandra Kasperczyk, Sławomir Kasperczyk, Department of Biochemistry, Medical University of Silesia in Katowice, Zabrze 41-808, Poland
Palok Aich, School of Biological Sciences, National Institute of Science Education and Research, Khurdha 752050, India
Shivaram P Singh, Department of Gastroenterology, SCB Medical College, Cuttack 753007, India
Author contributions: Bellanti F and Vendemiale G designed and coordinated the study; Bellanti, F, Lo Buglio A, Dobrakowsky M, and Kasperczyk A performed the experiments, acquired and analyzed data; Bellanti F, Lo Buglio A, Dobrakowsky M, Kasperczyk A, Kasperczyk S, Serviddio G, Singh SP, Aich P, and Vendemiale G interpreted the data; Bellanti F wrote the manuscript; Kasperczyk S, Serviddio G, Singh SP, Aich P, and Vendemiale G supervised the manuscript; and all authors approved the final version of the article.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board at the University of Foggia.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
STROBE statement: The Authors have read the STROBE statement - checklist of items, and the manuscript was prepared and revised according to the STROBE statement - checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Francesco Bellanti, MD, PhD, Associate Professor, Department of Medical and Surgical Sciences, University of Foggia, viale Pinto, 1, Foggia 71122, Italy. francesco.bellanti@unifg.it
Received: January 10, 2022
Peer-review started: January 10, 2022
First decision: March 8, 2022
Revised: March 18, 2022
Accepted: June 18, 2022
Article in press: June 18, 2022
Published online: July 14, 2022
ARTICLE HIGHLIGHTS
Research background

Clinical trials of sodium glucose cotransporter-2 inhibitors (SGLT2-I), recently approved drugs for type 2 diabetes (T2D), reported beneficial cardiovascular (CV) and renal outcomes.

Research motivation

Inflammation and oxidative stress are major causes of vascular dysfunction and CV disease in diabetes and pre-clinical studies demonstrated that SGLT2-I promote anti-inflammatory effects by lowering oxidative stress.

Research objectives

To investigate the effects of SGLT2-I on markers of oxidative stress, inflammation, liver steatosis, and fibrosis in patients of T2D with non-alcoholic fatty liver disease (NAFLD).

Research methods

Observational prospective study enrolling 52 consecutive outpatients treated with metformin monotherapy and exhibiting poor glycemic control, which were introduced to an SGLT2-I (n = 26) or a different hypoglycemic drug (n = 26). Circulating interleukins and serum hydroxynonenal (HNE)- or malondialdehyde (MDA)-protein adducts, fatty liver index (FLI), NAFLD fibrosis score, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio ratio, AST-to-platelet-ratio index (APRI), and fibrosis-4, as well as transient elastography (FibroScan) on the day before (T0) and following treatment for six months (T1) were evaluated.

Research results

With respect to other hypoglycemic drugs, treatment with SGLT2-I resulted in a reduction of FLI and APRI, as well as of the FibroScan result, as well as lower circulating levels of interleukins (IL)-1β, IL-6, tumor necrosis factor, vascular endothelial growth factor, and monocyte chemoattractant protein-1, higher levels of IL-4 and IL-10, decreased serum HNE- and MDA-protein adducts. Markers of circulating oxidative stress correlated with liver steatosis and fibrosis scores.

Research conclusions

This study indicates that, more than optimizing glucose control, treatment with SGLT2-I in patients with T2D and NAFLD is associated with improvement of liver steatosis and fibrosis markers and circulating pro-inflammatory and redox status.

Research perspectives

This study encourages extensive randomized controlled trials to confirm these preliminary observations, and basic investigations to define the molecular mechanisms underlying the effects of SGLT2-I in NAFLD.