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

Type2 Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03646292
• Other study ID #: 4-2018-0655
• Status: Recruiting
• Phase: Phase 4
• Start date: December 19, 2018
• Est. completion date: February 2021

Study information

• Verified date: October 2020
• Source: Yonsei University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: February 2021
• Est. primary completion date: February 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• NAFLD - Nonalcoholic Fatty Liver Disease
• Non-alcoholic Fatty Liver Disease
• Type2 Diabetes

Intervention

Drug:
• Pioglitazone
The investigators will compare the degree of liver fat between Pioglitazone monotherapy, Empagliflozin monotherapy, Combination of pioglitazone and empagliflozin following randomization.
• Empagliflozin
The investigators will compare the degree of liver fat between Pioglitazone monotherapy, Empagliflozin monotherapy, Combination of pioglitazone and empagliflozin following randomization.
• 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.

Locations

Country	Name	City	State
Korea, Republic of	Yonsei University College of Medicine, Department of Internal Medicine, Division of Endocrinology, Severance Hospital, Diabetes Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Yonsei University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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