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Brodosi et al. Hepatoma Res 2020;6:82 Hepatoma Research
DOI: 10.20517/2394-5079.2020.88

Review Open Access

Diabetes and NAFLD: a high-risk cohort with definite
therapeutic potential

Lucia Brodosi , Alessandra Musio , Francesca Alessandra Barbanti , Dorina Mita , Giulio Marchesini ,
1,2
1
1,2
1,2
1,2
Maria Letizia Petroni 1,2
1 Department of Medical and Surgical Sciences, “Alma Mater” University, Bologna 40138, Italy.
2 Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy.
Correspondence to: Dr. Lucia Brodosi, Azienda Ospedaliero-Universitaria di Bologna, via Albertoni 15, Bologna 40138, Italy.
E-mail: lucia.brodosi2@unibo.it
How to cite this article: Brodosi L, Musio A, Barbanti FA, Mita D, Marchesini G, Petroni ML. Diabetes and NAFLD: a high-risk
cohort with definite therapeutic potential. Hepatoma Res 2020;6:82. http://dx.doi.org/10.20517/2394-5079.2020.88
Received: 21 Aug 2020 First Decision: 23 Sep 2020 Revised: 30 Sep 2020 Accepted: 14 Oct 2020 Published: 5 Dec 2020

Academic Editor: Stefano Bellentani Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Abstract
Received: First Decision: Revised: Accepted: Published:
Despite the fact that non-alcoholic fatty liver disease (NAFLD) and its severe clinical forms [non-alcoholic
Science Editor: Copy Editor: Production Editor: Jing Yu steatohepatitis (NASH) and NASH-cirrhosis] are highly prevalent in the general population, there are no licensed
drugs for NAFLD, and lifestyle intervention remains the only treatment accepted by international guidelines. This
is despite massive investments in research by pharmaceutical companies. In the presence of type 2 diabetes,
novel anti-diabetic drugs offer an opportunity to reduce the burden of NAFLD, by adequate control of glucose
and lipid metabolism, also reducing the risk of NASH progression, advanced fibrosis, and finally hepatocellular
carcinoma. We extensively reviewed the literature, based either on registration studies, ad hoc randomized studies
or real-world data, to define the effectiveness of anti-diabetic drugs in the treatment of NAFLD and prevention of
hepatocellular carcinoma (HCC). Metformin provides the best evidence for decreased risk of HCC, pioglitazone
was associated with decreased progression to fibrosis, glucagon-like peptide-1 receptor agonists offer a possible
opportunity to reduce NAFLD progression coupled with a definite protection for cardiovascular outcomes, and
sodium-glucose cotransporter-2 inhibitors are likely to reduce lipid burden, simultaneously reducing the risk of
progressive renal and heart failure. For the latter two drug classes, the effects on NAFLD might largely explained
by decreased body weight, in keeping with the beneficial effects of intensive lifestyle intervention.

Keywords: Metformin, pioglitazone, incretins, DPP-4 inhibitors, GLP-1 receptor agonists, SGLT-2 inhibitors, insulin,
cirrhosis

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
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