SGLT-2 Inhibitors in NAFLD: Expanding Their Role beyond Diabetes and Cardioprotection?

Theodoros Androutsakos, Narjes Nasiri-Ansari, Athanasios-Dimitrios Bakasis, Ioannis Kyrou, Efstathios Efstathopoulos, Harpal S. Randeva, Eva Kassi

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    Non-alcoholic fatty liver disease (NAFLD) is an ‘umbrella’ term, comprising a spectrum ranging from benign, liver steatosis to non-alcoholic steatohepatitis, liver fibrosis and eventually cirrhosis and hepatocellular carcinoma. NAFLD has evolved as a major health problem in recent years. Discovering ways to prevent or delay the progression of NAFLD has become a global focus. Lifestyle modifications remain the cornerstone of NAFLD treatment, even though various pharmaceutical interventions are currently under clinical trial. Among them, sodium-glucose co-transporter type-2 inhibitors (SGLT-2i) are emerging as promising agents. Processes regulated by SGLT-2i, such as endoplasmic reticulum (ER) and oxidative stress, low-grade inflammation, autophagy and apoptosis are all implicated in NAFLD pathogenesis. In this review, we summarize the current understanding of the NAFLD pathophysiology, and specifically focus on the potential impact of SGLT-2i in NAFLD development and progression, providing current evidence from in vitro, animal and human studies. Given this evidence, further mechanistic studies would advance our understanding of the exact mechanisms underlying the pathogenesis of NAFLD and the potential beneficial actions of SGLT-2i in the context of NAFLD treatment.
    Original languageEnglish
    Article number3107
    Number of pages35
    JournalInternational Journal of Molecular Sciences
    Issue number6
    Publication statusPublished - 13 Mar 2022

    Bibliographical note

    Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( s/by/4.0/).


    • non-alcoholic fatty liver disease
    • NAFLD
    • MAFLD
    • SGLT-2
    • sodium-glucose co-transporter type-2 inhibitors
    • metabolic syndrome


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