Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Antidiabetic Therapy in the Treatment of NASH

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.

Journal reference: Int. J. Mol. Sci. 2020, 21, 1907
DOI: 10.3390/ijms21061907

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.

Subject Areas

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

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.