Hepatoprotective Effect of SGLT2 Inhibitor on Nonalcoholic Fatty Liver Disease

Sumida Y^1*, Yoneda M¹, Tokushige K², Kawanaka M³, Fujii H⁴, Yoneda M⁵, Imajo K⁵, Takahashi H⁶, Ono M⁷, Nozaki Y⁸, Hyogo H⁹, Koseki M¹⁰, Yoshida Y¹¹, Kawaguchi T¹², Kamada Y¹³, Eguchi Y¹⁴, Okanoue T¹⁵, Nakajima A⁵; Japan Study Group of NAFLD (JSG-NAFLD)¹⁶

¹Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Japan

²Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan

³Department of General Internal Medicine2, Kawasaki Medical School, Okayama 700-8505, Japan

⁴Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan

⁵Division of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan

⁶Department of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga, Japan

⁷Division of Gastroenterology and Hepatology, Department of Internal Medicine,Tokyo Women's Medical University Medical Center East, Tokyo, Japan

⁸Department of Gastroenterology, National Center for Global Health and Medicine, Tokyo, Japan

⁹Department of Gastroenterology, JA Hiroshima General Hospital, Japan

¹⁰Department of Cardiovascular Medicine, Department of Medicine, Osaka University Graduate School of Medicine

¹¹Department of Gastroenterology and Hepatology, Suita Municipal Hospital, Osaka, Japan

¹²Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan

¹³Department of Molecular Biochemistry & Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

¹⁴Liver Center, Saga University Hospital, Saga, Japan

¹⁵Hepatology Center, Saiseikai Suita Hospital, Osaka, Japan

¹⁶Japan Strategic Medical Administration Research Center, Nagoya, Aichi, Japan

Corresponding Author: Yoshio Sumida

Address: Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan; Tel: +81-561-62-3311; Fax: +81-561-62-1508; Email: sumida.yoshio.500@mail.aichi-med-u.ac.jp

Received date: 04 February 2020; Accepted date: 26 February 2020; Published date: 05 March 2020

Citation: Sumida Y, Yoneda M, Tokushige K, Kawanaka M, Fujii H, Yoneda M, Imajo K, Takahashi H, Ono M, Nozaki Y, Hyogo H, Koseki M, Yoshida Y, Kawaguchi T, Kamada Y, Eguchi Y, Okanoue T, Nakajima A; Japan Study Group of NAFLD (JSG-NAFLD). Hepatoprotective Effect of SGLT2 Inhibitor on Nonalcoholic Fatty Liver Disease. Diab Res. 2020 Mar 05;2(S1):17-25.

Copyright © 2020 Sumida Y, Yoneda M, Tokushige K, Kawanaka M, Fujii H, Yoneda M, Imajo K, Takahashi H, Ono M, Nozaki Y, Hyogo H, Koseki M, Yoshida Y, Kawaguchi T, Kamada Y, Eguchi Y, Okanoue T, Nakajima A; Japan Study Group of NAFLD (JSG-NAFLD). 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.

Keywords: Nonalcoholic Fatty Liver Disease; Sodium-glucose Cotransporter 2; Glucagon like Peptide-1; Hepatic Fibrosis; Hepatocarcinogenesis

Abstract

A fourth of the adult population is now suffering from nonalcoholic fatty liver disease (NAFLD) worldwide. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to liver-related mortality. NAFLD/NASH is closely associated with type 2 diabetes. Although pioglitazone is now recommended as the 1^st line therapy for NASH with type 2 diabetes, pioglitazone has several safety concerns such as body weight gain, heart failure, fluid retention, and bone fracture in women. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have a variety of functions such as glycemic control, bodyweight reduction, and decreased body pressure. Accumulating evidence has shown that this agent has also cardioprotective and renoprotective effects in patients with or without type 2 diabetes. Recent studies that SGLT2 inhibitor can also reduce in transaminase activities or hepatic fat content in NAFLD. NAFLD patients with type 2 diabetes can be indicated for SGLT2 inhibitor, because they are obese, have insulin resistance, and at high risk of cardiovascular events. The phase 3 study of dapagliflozin for NAFLD (DEAN study) is now ongoing. It remains unknown whether this agent can ameliorate hepatic fibrosis in NASH, leading to improved over-all or liver-related survival. Since the leading cause of NAFLD mortality is cardiovascular events, SGLT2 inhibitors will become the 1^st line treatment for NAFLD/NASH.