Effect of tofogliflozin and pioglitazone on hepatic steatosis in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus: A randomized, open-label pilot study (ToPiND study)

Anna Ozaki; Masato Yoneda; Takaomi Kessoku; Michihiro Iwaki; Takashi Kobayashi; Yasushi Honda; Yuji Ogawa; Kento Imajo; Eiji Sakai; Masataka Taguri; Takeharu Yamanaka; Tomoyuki Iwasaki; Takeo Kurihashi; Satoru Saito; Atsushi Nakajima

doi:10.1016/j.conctc.2019.100516

Effect of tofogliflozin and pioglitazone on hepatic steatosis in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus: A randomized, open-label pilot study (ToPiND study)

Contemp Clin Trials Commun. 2019 Dec 31:17:100516. doi: 10.1016/j.conctc.2019.100516. eCollection 2020 Mar.

Authors

Anna Ozaki¹, Masato Yoneda¹, Takaomi Kessoku^{1

2}, Michihiro Iwaki¹, Takashi Kobayashi¹, Yasushi Honda^{1

2}, Yuji Ogawa¹, Kento Imajo¹, Eiji Sakai¹, Masataka Taguri³, Takeharu Yamanaka⁴, Tomoyuki Iwasaki⁵, Takeo Kurihashi⁶, Satoru Saito¹, Atsushi Nakajima¹

Affiliations

¹ Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
² Department of Palliative Care Center Yokohama City University Hospital, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
³ Department of Data Science, Yokohama City University School of Data Science, 2-22 Seto, Kanazawa-ku, Yokohama, 236-0027, Japan.
⁴ Department of Biostatistics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
⁵ Iwasaki Internal Medicine Clinic, 1-1-5 Furu-ruyokohama1F, Kamihoshikawa, Hodogaya-ku, Yokohama, Kanagawa, 240-0042, Japan.
⁶ Department of Internal Medicine, Yokohama Clinic, Kanagawa Dental University, 3-31-6 Tsuruya-cho, Kanagawa, Yokohama, Kanagawa, 221-0835, Japan.

Abstract

Background: The incidence of nonalcoholic fatty liver disease (NAFLD) has increased recently and is related to obesity and the associated surge in type 2 diabetes mellitus (DM) and metabolic syndrome diagnoses. We aim to compare the effectiveness of tofogliflozin and pioglitazone treatment on hepatic steatosis in patients with NAFLD with type 2 DM.

Methods: This is an open label, prospective, randomized exploratory study. Patients who meet the inclusion criteria and do not meet any exclusion criteria will undergo magnetic resonance imaging (MRI)-based proton density fat fraction (MRI-PDFF). Patients with ≥10% liver fat content on MRI-PDFF will be randomly assigned to receive tofogliflozin 20 mg per day (n = 20) or pioglitazone 15-30 mg per day (n = 20). MRI will be performed after 24 weeks following initiation of medication therapy. Then, patients will take tofogliflozin and pioglitazone in combination in both groups for 24 weeks. MRI will be performed again at 48 weeks (24 weeks after initiation medication in combination).

Results: Our study's primary endpoint will be change in hepatic steatosis measured by MRI-PDFF at 24 weeks after medication therapy. The secondary endpoint will be change in alanine aminotransferase at 24 weeks of medication therapy and the main exploratory endpoint will be changes in liver fat content and liver sclerosis at 48 weeks of medication.

Conclusions: We will compare the effectiveness of tofogliflozin and pioglitazone treatment using MRI for improving hepatic steatosis in patients with NAFLD complicated by DM and investigate if the combination of these two medications is effective for treating NAFLD.

Trial registration: This trial is registered in the Japan Registry of Clinical Trials (jRCTs031180159).

Protocol version: 1.2, 14 December 2018.

Keywords: AE, adverse event; ALT, alanine aminotransferase; CRF, case report form; DM, diabetes mellitus; Diabetes mellitus; FAS, full analysis set; HbA1c, glycated hemoglobin; Hepatic steatosis; MRI-Based proton density fat fraction; MRI-PDFF, magnetic resonance imaging-based proton density fat fraction; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; Non-alcoholic fatty liver disease; PPS, per protocol set; Pioglitazone; SPIRIT, the Standard Protocol Items: Recommendations for Interventional Trials; Tofogliflozin; jRCTs, the Japan Registry of Clinical Trials.