Comparison of The Effects of Thiazolidinediones(TZD), Sodium- Glucose Cotransporter 2 Inhibitors(SGLT2i) Alone and TZD / SGLT2i Combination Therapy on Non-alcoholic Fatty Liver Disease in Type 2 Diabetic Patients With Fatty Liver

To investigate the synergic therapeutic effect of thiazolidinediones and SGLT2 inhibitor on nonalcoholic fatty liver disease, the effect of empagliflozin 10mg, pioglitazone 15mg monotherapy and combination therapy n patients with type 2 diabetes and fatty liver will be compared and analyzed.

This study included a total of 60 patients (20 per subgroup) for randomized controlled trials with prospective, open label, randomized, single-institution clinical trials.

The drug will be maintained for a total of six months. The primary endpoint is the difference of liver fat change measured by MRI-PDFF in co-localized regions of interest within nine liver segments between three groups.

Study Overview

• Status: Unknown
• Conditions: Type2 Diabetes; NAFLD - Nonalcoholic Fatty Liver Disease
• Intervention / Treatment: Drug: Pioglitazone; Drug: Empagliflozin; Drug: Combination of pioglitazone and empagliflozin

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Yonsei University College of Medicine, Department of internal Medicine, Division of Endocrinology, Severance Hospital, Diabetes Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men or women aged 19 years or over, under 75 years
• A person diagnosed with nonalcoholic fatty liver in abdominal ultrasound (abdominal ultrasound can be substituted if there is a diagnosis of fatty liver through ultrasound within 1 year), or a person diagnosed with fatty liver in abdominal ultrasonography through screening because of clinical suspicion of fatty liver
• Patients who are diagnosed with type 2 diabetes and who are treated with oral medication, excluding TZD or SGLT2i drug users within the last 12 weeks
• Those who have voluntarily agreed in written form to participate in the clinical trial after hearing the explanation of this clinical trial
• Those who understand the content of the clinical trial and are able to participate in the trial until the end of the clinical trial

Exclusion Criteria:

• Diabetic patients other than type 2 diabetes, including type 1 diabetes and gestational diabetes
• Type 2 diabetic patients undergoing insulin therapy
• Patients who have taken TZD or SGLT2i drugs within the last 12 weeks or have had a history of severe side effects after taking the above drugs
• Patients with acute or chronic metabolic acidosis, including diabetic ketoacidosis with or without coma, and those with a history of ketone phosphatemia (within 6 months)
• Patients who meet the criteria for alcoholic liver disease (210 g / week for men in the last two years, 140 g / week for women)
• People who take drugs that can cause fatty liver (amiodarone, methotrexate, tamoxifen, valproate, etc.)
• Allergic or hypersensitive to the drug or its constituents
• Patients receiving oral or parenteral corticosteroid therapy chronic (within consecutive 14 days) within 8 weeks prior to screening require continual changes in corticosteroid dosage for therapeutic purposes
• Patients with genetic problems such as galactosemia, Lapp lactase deficiency or glucose-galactose uptake
• Malignant tumors that are currently undergoing treatment or progressive
• Patients with a history of substance abuse or alcohol intoxication within 12 weeks
• Human immunodeficiency virus (HIV)
• Patients with severe infection, pre- and post-operative, and severe trauma
• Patients with cardiac failure within 6 months (class III to IV in the NYHA classification)
• Patients with acute cardiovascular disease within 12 weeks (patients with unstable angina, myocardial infarction, transient ischemic attack, cerebrovascular disease, coronary artery bypass grafting, or coronary intervention)
• People with renal failure, chronic renal disease (estimated glomerular filtration rate <45 mL / min / 1.73 m2) or those who are difficult to use the medication due to dialysis
• Pregnant or lactating women
• A person who the examiner considers not eligible for clinical trials

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Pioglitazone monotherapy; Pioglitazone 15mg 1T daily for 6 months	Drug: Pioglitazone; The investigators will compare the degree of liver fat between Pioglitazone monotherapy, Empagliflozin monotherapy, Combination of pioglitazone and empagliflozin following randomization.
EXPERIMENTAL: Empagliflozin monotherapy; Empagliflozin 10mg 1T daily for 6 months	Drug: Empagliflozin; The investigators will compare the degree of liver fat between Pioglitazone monotherapy, Empagliflozin monotherapy, Combination of pioglitazone and empagliflozin following randomization.
EXPERIMENTAL: Pioglitazone + Empagliflozin combination therapy; Pioglitazone 15mg + Empagliflozin 10mg combination 1T daily for 6 months	Drug: Combination of pioglitazone and empagliflozin; The investigators will compare the degree of liver fat between Pioglitazone monotherapy, Empagliflozin monotherapy, Combination of pioglitazone and empagliflozin following randomization.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
liver fat change measured by MRI-PDFF in co-localized regions of interest within each of nine liver segments	MRI is used to measure the fat fraction in 9 liver segments, and this test has been reported to be more sensitive than the biopsy-based steatosis grade assessment in confirming liver fat changes in previous studies	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver fibrosis measured by magnetic resonance elastography	The secondary endpoint is to analyze the changes before and after drug administration for the following items: Liver fibrosis measured by magnetic resonance elastography	6 months
The changes in lipid profile	The secondary endpoint is to analyze the changes before and after drug administration for the following items: The changes in lipid profile including LDL-C, TG, HDL, TC	6 months
The changes in liver enzyme	The secondary endpoint is to analyze the changes before and after drug administration for the following items: The changes in liver enzyme including ALT, AST, GGT	6 months
The changes in glucose metabolism	The secondary endpoint is to analyze the changes before and after drug administration for the following items: The changes in glucose metabolism including HOMAIR, fasting glucose, HbA1c, fasting insulin	6 months
The changes in inflammation status	The secondary endpoint is to analyze the changes before and after drug administration for the following items: The changes in inflammation status including CRP, other biomarker	6 months

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 19, 2018
• Primary Completion (ANTICIPATED): February 1, 2021
• Study Completion (ANTICIPATED): February 1, 2021

Study Registration Dates

• First Submitted: August 10, 2018
• First Submitted That Met QC Criteria: August 22, 2018
• First Posted (ACTUAL): August 24, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 19, 2020
• Last Update Submitted That Met QC Criteria: October 15, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Pioglitazone; Empagliflozin
• Other Study ID Numbers: 4-2018-0655

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No