Efficacy of peroxisome proliferator-activated receptor agonists, glucagon-like peptide-1 receptor agonists or sodium-glucose cotransporter-2 inhibitors for treatment of non-alcoholic fatty liver disease: A systematic review

There are no licensed treatments for non-alcoholic fatty liver disease (NAFLD), but three different classes of antihyperglycaemic drugs—peroxisome proliferator-activated receptor (PPAR) agonists, glucagon-like peptide-1 receptor (GLP-1R) agonists, and sodium-glucose cotransporter-2 (SGLT2) inhibitors—show promise in the treatment of the disease. We did a systematic review of randomised controlled trials examining the efficacy of PPAR agonists, GLP-1R agonists, or SGLT2 inhibitors for specifically treating NAFLD in adults with or without type 2 diabetes. A total of 25 active-controlled or placebo-controlled trials met our inclusion criteria: eight for PPAR agonists, ten for GLP-1R agonists, and seven for SGLT2 inhibitors. 2597 individuals (1376 [53%] men vs 1221 [47%] women; mean age 52 years (SD 6); mean BMI 32 kg/m ² (SD 3); 1610 [62%] with type 2 diabetes) were included. Pioglitazone, lanifibranor, and GLP1-R agonists (mostly liraglutide and semaglutide) improved individual histological features of NASH (ie, steatosis, ballooning, lobular inflammation) or achieved resolution of NASH without worsening of fibrosis. SGLT2 inhibitors (mostly empagliflozin and dapagliflozin) reduced liver fat content, as assessed by magnetic resonance-based techniques.

10.1016/S2468-1253(21)00261-2

2468-1253

367-378

Mantovani, Alessandro

742fbaa2-6c99-4025-84b5-be1dbe9e56ce

Byrne, Christopher

1370b997-cead-4229-83a7-53301ed2a43c

Targher, Giovanni

043e0811-b389-4922-974e-22e650212c5f

11 January 2022

Mantovani, Alessandro

742fbaa2-6c99-4025-84b5-be1dbe9e56ce

Byrne, Christopher

1370b997-cead-4229-83a7-53301ed2a43c

Targher, Giovanni

043e0811-b389-4922-974e-22e650212c5f

Mantovani, Alessandro, Byrne, Christopher and Targher, Giovanni (2022) Efficacy of peroxisome proliferator-activated receptor agonists, glucagon-like peptide-1 receptor agonists or sodium-glucose cotransporter-2 inhibitors for treatment of non-alcoholic fatty liver disease: A systematic review. The Lancet Gastroenterology & Hepatology, 7 (4), 367-378. (doi:10.1016/S2468-1253(21)00261-2).

Record type: Review

Abstract

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Table 1_PPAR - Accepted Manuscript

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Accepted/In Press date: 12 July 2021

e-pub ahead of print date: 11 January 2022

Published date: 11 January 2022

Additional Information: Funding Information: CDB is supported in part by grants from the Southampton National Institute for Health Research Biomedical Research Centre, outside of the submitted work. GT is supported in part by grants from the University School of Medicine of Verona, Verona, Italy, outside of the submitted work. AM declares no competing interests. Publisher Copyright: © 2022 Elsevier Ltd Copyright: Copyright 2022 Elsevier B.V., All rights reserved.