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Open AccessReview

Antidiabetic Therapy in the Treatment of Nonalcoholic Steatohepatitis

1
Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan
2
Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University, Tokyo 162-8666, Japan
3
Department of General Internal Medicine2, Kawasaki Medical School, Okayama 700-8505, Japan
4
Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka 558-8585, Japan
5
Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan
6
Department of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga 840-8502, Japan
7
Liver Center, Saga University Hospital, Saga 840-8502, Japan
8
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokyo Women’s Medical University Medical Center East, Tokyo 116-8567, Japan
9
Department of Gastroenterology, National Center for Global Health and Medicine, Tokyo 162-8655, Japan
10
Department of Gastroenterology, JA Hiroshima General Hospital, Hiroshima 738-8503, Japan
11
Division of Cardiovascular Medicine, Department of Medicine, Osaka University Graduate School of Medicine, Suita Osaka 565-0871, Japan
12
Department of Gastroenterology and Hepatology, Suita Municipal Hospital, Osaka 564-8567, Japan
13
Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan
14
Department of Molecular Biochemistry & Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
15
Hepatology Center, Saiseikai Suita Hospital, Osaka 564-0013, Japan
*
Author to whom correspondence should be addressed.
Members are listed at the Acknowledgments.
Int. J. Mol. Sci. 2020, 21(6), 1907; https://doi.org/10.3390/ijms21061907
Received: 15 January 2020 / Revised: 4 March 2020 / Accepted: 5 March 2020 / Published: 11 March 2020
(This article belongs to the Special Issue Diabetic Liver Disease)
Liver-related diseases are the third-leading causes (9.3%) of mortality in type 2 diabetes (T2D) in Japan. T2D 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. No pharmacotherapies are established for NASH patients with T2D. Though vitamin E is established as a first-line agent for NASH without T2D, its efficacy for NASH with T2D recently failed to be proven. The effects of pioglitazone on NASH histology with T2D 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 and NAFLD (LEAN study, LEAD trial, and E-LIFT study). Among a variety of SGLT2 inhibitors, dapagliflozin has already entered the phase 3 trial (DEAN study). A key clinical need is to determine the kinds of antidiabetic drugs that are the most appropriate for the treatment of NASH to prevent the progression of hepatic fibrosis, resulting in HCC or liver-related mortality without increasing the risk of cardiovascular or renal events. Combination therapies, such as glucagon receptor agonist/GLP-1 or gastrointestinal peptide/GLP-1, are under development. This review focused on antidiabetic agents and future perspectives on the view of the treatment of NAFLD with T2D. View Full-Text
Keywords: dipeptidyl peptidase-4; fibroblast growth factor; gastrointestinal peptide; glucagon-like peptide 1; glucagon receptor; peroxisome proliferator-activated receptor; sodium glucose cotransporter dipeptidyl peptidase-4; fibroblast growth factor; gastrointestinal peptide; glucagon-like peptide 1; glucagon receptor; peroxisome proliferator-activated receptor; sodium glucose cotransporter
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MDPI and ACS Style

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.; Japan Study Group of NAFLD. Antidiabetic Therapy in the Treatment of Nonalcoholic Steatohepatitis. Int. J. Mol. Sci. 2020, 21, 1907. https://doi.org/10.3390/ijms21061907

AMA Style

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, Japan Study Group of NAFLD. Antidiabetic Therapy in the Treatment of Nonalcoholic Steatohepatitis. International Journal of Molecular Sciences. 2020; 21(6):1907. https://doi.org/10.3390/ijms21061907

Chicago/Turabian Style

Sumida, Yoshio; Yoneda, Masashi; Tokushige, Katsutoshi; Kawanaka, Miwa; Fujii, Hideki; Yoneda, Masato; Imajo, Kento; Takahashi, Hirokazu; Eguchi, Yuichiro; Ono, Masafumi; Nozaki, Yuichi; Hyogo, Hideyuki; Koseki, Masahiro; Yoshida, Yuichi; Kawaguchi, Takumi; Kamada, Yoshihiro; Okanoue, Takeshi; Nakajima, Atsushi; Japan Study Group of NAFLD. 2020. "Antidiabetic Therapy in the Treatment of Nonalcoholic Steatohepatitis" Int. J. Mol. Sci. 21, no. 6: 1907. https://doi.org/10.3390/ijms21061907

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