Letter to the Editor Open Access
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Oct 15, 2021; 12(10): 1809-1811
Published online Oct 15, 2021. doi: 10.4239/wjd.v12.i10.1809
Non-alcoholic fatty liver disease, diabetes medications and blood pressure
Ioannis Ilias, Costas Thomopoulos
Ioannis Ilias, Department of Endocrinology, Diabetes and Metabolism, Elena Venizelou Hospital, Athens 11521, Greece
Costas Thomopoulos, Department of Cardiology, Elena Venizelou Hospital, Athens 11521, Greece
ORCID number: Ioannis Ilias (0000-0001-5718-7441); Costas Thomopoulos (0000-0002-8491-6029).
Author contributions: Both Ilias I and Thomopoulos C conceived this work, performed the literature research, wrote this letter and revised it.
Conflict-of-interest statement: The authors declare no conflict of interest.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ioannis Ilias, MD, PhD, Consultant Physician-Scientist, Department of Endocrinology, Diabetes and Metabolism, Elena Venizelou Hospital, 2, El Venizelou Square, Athens 11521, Greece. iiliasmd@yahoo.com
Received: May 23, 2021
Peer-review started: May 23, 2021
First decision: June 16, 2021
Revised: June 22, 2021
Accepted: September 6, 2021
Article in press: September 6, 2021
Published online: October 15, 2021

Abstract

New glucose-lowering agents reduce liver enzyme levels and blood pressure (BP). Whether this finding can be extended to non-alcoholic fatty liver disease (NAFLD) patients, in whom a bidirectional association of NAFLD measures and BP has been also demonstrated, remains by and large unknown.

Key Words: Antidiabetic drugs, Blood pressure reduction, Non-alcoholic fatty liver disease, Sodium glucose cotransporter 2, Alanine aminotransferase, Aspartate aminotransferase

Core Tip: All new glucose-lowering agents reduce liver enzyme levels. Additionally, sodium glucose cotransporter 2 inhibitors can reduce both systolic and diastolic blood pressure (BP) by 3.5/1 mmHg, respectively, while glucagon-like peptide-1 agonist treatment was accompanied by systolic BP reduction of 1 mmHg. Whether this previous finding can be extended to non-alcoholic fatty liver disease (NAFLD) patients, in whom a bidirectional association of NAFLD measures and BP has been also demonstrated, remains by and large unknown.



TO THE EDITOR

We read with interest the meta-analysis by Fu et al[1], which aimed to investigate the changes from baseline of selective liver enzymes, namely alanine aminotransferase and/or aspartate aminotransferase, in patients with non-alcoholic fatty liver disease (NAFLD). Patients were treated with either new glucose-lowering agents [i.e., dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor (GLP-1) agonists, and sodium glucose cotransporter 2 (SGLT2) inhibitors] or placebo/other glucose-lowering drugs. Secondary outcomes along with the same comparison were changes from baseline of (1) different measures of body adiposity partly estimated by liver magnetic resonance, and (2) glycated hemoglobin levels. The authors clearly showed[1] that all new glucose-lowering agents reduced liver enzyme levels, whereas measures of body adiposity including body fat composition were at least numerically reduced in all cases. It would be interesting to know the changes of fatty liver index[2-4], which is a more integrated measure of liver damage in NAFLD, and whether new glucose-lowering agents can effectively reduce blood pressure (BP) levels in this pool of studies. The effect of new glucose-lowering agents against placebo on BP levels has been investigated in a pool of outcome trials[5], suggesting that among these agents, only SGLT2 inhibitors can reduce both systolic and diastolic BP by 3.5/1 mmHg, respectively, while GLP-1 agonist treatment was accompanied by systolic BP reduction of 1 mmHg. Whether this previous finding[5] can be extended to NAFLD patients, in whom a bidirectional association of NAFLD measures and BP has been also demonstrated[6], remains by and large unknown.

Beyond the above clinical considerations, we would like to emphasize on some technical issues regarding the meta-analysis by Fu et al[1]. First, the authors estimated changes from baseline and not differences after the intervention. Differences from baseline can bias the results in two ways, (1) because of Wilder’s principle[7], indicating that reductions are higher from higher baseline levels, and (2) because in randomized studies with a limited number of participants, the levels of a given measure are not identical between treatment arms[8]. Second, another source of bias is the inclusion of placebo-controlled and active-controlled studies[9]. Although placebo is a fair comparator in this type of investigation, active-controls may have reduced the net outcome effect of new glucose-lowering agents. Third, wandering between statistical models (i.e., fixed-effect vs random-effects) is not advised in clinical meta-analyses and a random-effects model, when gathering studies from the literature, should always - a priori - be selected irrespectively of the underlying heterogeneity[10].

The study by Fu et al[1] is clinically important and suggests that new glucose-lowering agents contribute to a reduction of NAFLD severity, which may partially explain the cardioprotective effect of these drugs on major outcomes[5,11].

Footnotes

Manuscript source: Invited manuscript

Specialty type: Endocrinology and metabolism

Country/Territory of origin: Greece

Peer-review report’s scientific quality classification

Grade A (Excellent): 0

Grade B (Very good): B, B

Grade C (Good): 0

Grade D (Fair): 0

Grade E (Poor): 0

P-Reviewer: Li CP, Mrzljak A S-Editor: Gao CC L-Editor: A P-Editor: Wang LYT

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