Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Antidiabetic Therapy in the Treatment of NASH

Yoshio Sumida
* ORCID logo ,
Masashi Yoneda
,
Katsutoshi Tokushige
,
Miwa Kawanaka
,
Hideki Fujii
,
Masato Yoneda
,
Kento Imajo
ORCID logo ,
Hirokazu Takahashi
,
Yuichiro Eguchi
,
Masafumi Ono
,
Yuichi Nozaki
,
Hideyuki Hyogo
,
Masahiro Koseki
,
Yuichi Yoshida
,
Takumi Kawaguchi
ORCID logo ,
Yoshihiro Kamada
,
Takeshi Okanoue
,
Atsushi Nakajima
Version 1 : Received: 15 January 2020 / Approved: 16 January 2020 / Online: 16 January 2020 (11:44:49 CET)

A peer-reviewed article of this Preprint also exists.

Sumida, Y.; Yoneda, M.; Tokushige, K.; Kawanaka, M.; Fujii, H.; Yoneda, M.; Imajo, K.; Takahashi, H.; Eguchi, Y.; Ono, M.; Nozaki, Y.; Hyogo, H.; Koseki, M.; Yoshida, Y.; Kawaguchi, T.; Kamada, Y.; Okanoue, T.; Nakajima, A.; (JSG-NAFLD), J.S.G.N. Antidiabetic Therapy in the Treatment of Nonalcoholic Steatohepatitis. Int. J. Mol. Sci. 2020, 21, 1907. Sumida, Y.; Yoneda, M.; Tokushige, K.; Kawanaka, M.; Fujii, H.; Yoneda, M.; Imajo, K.; Takahashi, H.; Eguchi, Y.; Ono, M.; Nozaki, Y.; Hyogo, H.; Koseki, M.; Yoshida, Y.; Kawaguchi, T.; Kamada, Y.; Okanoue, T.; Nakajima, A.; (JSG-NAFLD), J.S.G.N. Antidiabetic Therapy in the Treatment of Nonalcoholic Steatohepatitis. Int. J. Mol. Sci. 2020, 21, 1907.

Abstract

Liver related diseases are the 3rd leading causes (9.3%) of mortality in type 2 diabetes mellitus (T2DM) in Japan. T2DM is closely associated with nonalcoholic fatty liver disease (NAFLD) which is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma (HCC) and hepatic failure. There are no established pharmacotherapies for NASH patients with T2DM. Though vitamin E is established as a 1st line agent in NASH without T2DM, its efficacy was recently denied in NASH with T2DM. The effects of pioglitazone on NASH histology with T2DM have extensively been established, but several concerns exist such as body weight gain, fluid retention, cancer incidence, and bone fracture. Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium/glucose cotransporter 2 (SGLT2) inhibitors are expected to ameliorate NASH　(LEAN study, LEAD trial, and E-LIFT study). Among a variety of SGLT2 inhibitors, dapagliflozin have already entered phase 3 trials (DEAN study). A key clinical question is what kinds of anti-diabetic drugs are the most appropriate for the treatment of NASH to prevent progression of hepatic fibrosis resulting in HCC/liver-related mortality without increasing risk at cardiovascular or renal events. The combination therapies such as glucagon receptor agonist/GLP-1 or gastrointestinal peptide /GLP-1 will be under development. This review focuses on antidiabetic agents and future perspectives on the view of the treatment of NAFLD with T2DM.

Keywords

Dipeptidyl peptidase-4; Fibroblast growth factor; Gastrointestinal peptide; Glucagon-like peptide 1; Glucagon receptor; Peroxisome proliferator-activated receptor; Sodium glucose cotransporter

Subject

Medicine and Pharmacology, Dietetics and Nutrition

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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