Comparing the effects of tofogliflozin and pioglitazone in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus (ToPiND study): a randomized prospective open-label controlled trial

Introduction The treatment of diabetes has a significant impact on the pathogenesis of non-alcoholic fatty liver disease (NAFLD). We compared the effectiveness of tofogliflozin, a selective sodium-glucose cotransporter 2 inhibitor, and pioglitazone for the treatment of NAFLD patients with type 2 dia...

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Main Authors: Atsushi Nakajima, Takeharu Yamanaka, Yasushi Honda, Kento Imajo, Masataka Taguri, Masato Yoneda, Yuji Ogawa, Takaomi Kessoku, Takashi Kobayashi, Anna Ozaki, Asako Nogami, Hiroyuki Kirikoshi, Tomoyuki Iwasaki, Takeo Kurihashi, Satoru Saito
Format: Article
Language:English
Published: BMJ Publishing Group 2021-03-01
Series:BMJ Open Diabetes Research & Care
Online Access:https://drc.bmj.com/content/9/1/e001990.full
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author Atsushi Nakajima
Takeharu Yamanaka
Yasushi Honda
Kento Imajo
Masataka Taguri
Masato Yoneda
Yuji Ogawa
Takaomi Kessoku
Takashi Kobayashi
Anna Ozaki
Asako Nogami
Hiroyuki Kirikoshi
Tomoyuki Iwasaki
Takeo Kurihashi
Satoru Saito
author_facet Atsushi Nakajima
Takeharu Yamanaka
Yasushi Honda
Kento Imajo
Masataka Taguri
Masato Yoneda
Yuji Ogawa
Takaomi Kessoku
Takashi Kobayashi
Anna Ozaki
Asako Nogami
Hiroyuki Kirikoshi
Tomoyuki Iwasaki
Takeo Kurihashi
Satoru Saito
author_sort Atsushi Nakajima
collection DOAJ
description Introduction The treatment of diabetes has a significant impact on the pathogenesis of non-alcoholic fatty liver disease (NAFLD). We compared the effectiveness of tofogliflozin, a selective sodium-glucose cotransporter 2 inhibitor, and pioglitazone for the treatment of NAFLD patients with type 2 diabetes mellitus.Research design and methods This open-label, prospective, single-center, randomized clinical trial recruited NAFLD patients with type 2 diabetes mellitus and a hepatic fat fraction of at least 10% as assessed based on the MRI-proton density fat fraction (MRI-PDFF). Eligible patients were stratified according to hemoglobin A1c (HbA1c), alanine transaminase, and MRI-PDFF levels and randomly assigned (1:1) to receive either 20 mg tofogliflozin or 15–30 mg pioglitazone, orally, once daily for 24 weeks. The primary endpoint was an absolute change in MRI-PDFF at 24 weeks. Efficacy and safety was assessed in all treated patients. This trial was registered in the Japan Registry of Clinical Trials.Results Overall, 40 eligible patients were randomly assigned to receive tofogliflozin (n=21) or pioglitazone (n=19). Changes in hepatic steatosis after 24 weeks of treatment were evaluated by MRI-PDFF, which showed a significant decrease in both groups (−7.54% (p<0.0001) and −4.12% (p=0.0042) in the pioglitazone and tofogliflozin groups, respectively). Compared with baseline, the body weight decreased by 2.83±2.86 kg (−3.6%, p=0.0443) in the tofogliflozin group and increased by 1.39±2.62 kg (1.7%, p=0.0002) in the pioglitazone group after 24 weeks. No life-threatening events or treatment-related deaths occurred.Conclusions Tofogliflozin was well tolerated, and it reduced the MRI-PDFF levels in NAFLD patients with type 2 diabetes mellitus.Trial registration number jRCTs031180159.
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spelling doaj-art-0d6788ef92d64108ab4f569c20631cd02024-12-12T13:10:13ZengBMJ Publishing GroupBMJ Open Diabetes Research & Care2052-48972021-03-019110.1136/bmjdrc-2020-001990Comparing the effects of tofogliflozin and pioglitazone in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus (ToPiND study): a randomized prospective open-label controlled trialAtsushi Nakajima0Takeharu Yamanaka1Yasushi Honda2Kento Imajo3Masataka Taguri4Masato Yoneda5Yuji Ogawa6Takaomi Kessoku7Takashi Kobayashi8Anna Ozaki9Asako Nogami10Hiroyuki Kirikoshi11Tomoyuki Iwasaki12Takeo Kurihashi13Satoru Saito14Department of Gastroenterology and Hepatology, Yokohama City University, Yokohama, Japan4 Department of Biostatics, Yokohama City University, Yokohama, Japanprofessor emeritus3 Department of Gastroenterology, Shin Yurigaoka General Hospital, Kawasaki, Kanagawa, Japan6 Department of Data Science, School of Data Science, Yokohama City University, Yokohama, Japan1 Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine Graduate School of Medicine, Yokohama, Kanagawa, JapanDepartment of Gastroenterology and Hepatology, Yokohama City University, Yokohama, JapanDepartment of Gastroenterology and Hepatology, Yokohama City University School of Medicine Graduate School of Medicine, Yokohama, Japan1 Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine Graduate School of Medicine, Yokohama, Kanagawa, JapanDepartment of Gastroenterology and Hepatology, Yokohama City University School of Medicine Graduate School of Medicine, Yokohama, Japan1 Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine Graduate School of Medicine, Yokohama, Kanagawa, JapanClinical Laboratory Department, Yokohama City University, Yokohama, Japan6 Department of Internal Medicine, Iwasaki Naika Clinic, Yokohama, Japan7 Department of Internal Medicine, Kanagawa Dental University Yokohama Clinic, Yokohama, JapanDepartment of Gastroenterology and Hepatology, Yokohama City University School of Medicine Graduate School of Medicine, Yokohama, JapanIntroduction The treatment of diabetes has a significant impact on the pathogenesis of non-alcoholic fatty liver disease (NAFLD). We compared the effectiveness of tofogliflozin, a selective sodium-glucose cotransporter 2 inhibitor, and pioglitazone for the treatment of NAFLD patients with type 2 diabetes mellitus.Research design and methods This open-label, prospective, single-center, randomized clinical trial recruited NAFLD patients with type 2 diabetes mellitus and a hepatic fat fraction of at least 10% as assessed based on the MRI-proton density fat fraction (MRI-PDFF). Eligible patients were stratified according to hemoglobin A1c (HbA1c), alanine transaminase, and MRI-PDFF levels and randomly assigned (1:1) to receive either 20 mg tofogliflozin or 15–30 mg pioglitazone, orally, once daily for 24 weeks. The primary endpoint was an absolute change in MRI-PDFF at 24 weeks. Efficacy and safety was assessed in all treated patients. This trial was registered in the Japan Registry of Clinical Trials.Results Overall, 40 eligible patients were randomly assigned to receive tofogliflozin (n=21) or pioglitazone (n=19). Changes in hepatic steatosis after 24 weeks of treatment were evaluated by MRI-PDFF, which showed a significant decrease in both groups (−7.54% (p<0.0001) and −4.12% (p=0.0042) in the pioglitazone and tofogliflozin groups, respectively). Compared with baseline, the body weight decreased by 2.83±2.86 kg (−3.6%, p=0.0443) in the tofogliflozin group and increased by 1.39±2.62 kg (1.7%, p=0.0002) in the pioglitazone group after 24 weeks. No life-threatening events or treatment-related deaths occurred.Conclusions Tofogliflozin was well tolerated, and it reduced the MRI-PDFF levels in NAFLD patients with type 2 diabetes mellitus.Trial registration number jRCTs031180159.https://drc.bmj.com/content/9/1/e001990.full
spellingShingle Atsushi Nakajima
Takeharu Yamanaka
Yasushi Honda
Kento Imajo
Masataka Taguri
Masato Yoneda
Yuji Ogawa
Takaomi Kessoku
Takashi Kobayashi
Anna Ozaki
Asako Nogami
Hiroyuki Kirikoshi
Tomoyuki Iwasaki
Takeo Kurihashi
Satoru Saito
Comparing the effects of tofogliflozin and pioglitazone in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus (ToPiND study): a randomized prospective open-label controlled trial
BMJ Open Diabetes Research & Care
title Comparing the effects of tofogliflozin and pioglitazone in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus (ToPiND study): a randomized prospective open-label controlled trial
title_full Comparing the effects of tofogliflozin and pioglitazone in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus (ToPiND study): a randomized prospective open-label controlled trial
title_fullStr Comparing the effects of tofogliflozin and pioglitazone in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus (ToPiND study): a randomized prospective open-label controlled trial
title_full_unstemmed Comparing the effects of tofogliflozin and pioglitazone in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus (ToPiND study): a randomized prospective open-label controlled trial
title_short Comparing the effects of tofogliflozin and pioglitazone in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus (ToPiND study): a randomized prospective open-label controlled trial
title_sort comparing the effects of tofogliflozin and pioglitazone in non alcoholic fatty liver disease patients with type 2 diabetes mellitus topind study a randomized prospective open label controlled trial
url https://drc.bmj.com/content/9/1/e001990.full
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