Antidiabetic Drugs for Steatotic Liver Disease

March 3, 2025 updated by: Yonsei University

Comparison of The Effects of Thiazolidinediones(TZD), Sodium- Glucose Cotransporter 2 Inhibitors(SGLT2i) Alone and TZD / SGLT2i Combination Therapy on Metabolic Dysfunction-Associated Steatotic Liver Disease in Patients With Type 2 Diabetes

To investigate the synergic therapeutic effect of thiazolidinediones and SGLT2 inhibitor on metabolic dysfunction-associated steatotic liver disease, the effect of empagliflozin 10mg, pioglitazone 15mg monotherapy and combination therapy in patients with type 2 diabetes and steatotic liver disease will be compared and analyzed.

This study was designed to include 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 24 weeks. The primary endpoint is the difference of liver fat change measured by MRI-PDFF in the largest possible polygonal region of interest encompassing both lobes of the liver between three groups.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
51

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Seoul, Korea, Republic of, 03722
        • Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

19 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Men and women aged 19 to 75 years
  2. Individuals who are diagnosed with type 2 diabetes (HbA1c ≥ 7.5% and < 11.0%) and treated with antidiabetic drugs excluding TZD and SGLT2i over the previous 12 weeks
  3. Individuals diagnosed with steatotic liver disease as documented by abdominal ultrasonography within the previous year
  4. Individuals who have voluntarily agreed in written form to participate in the clinical trial after hearing the explanation of this clinical trial
  5. Individuals 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:

  1. Type 1 diabetes and gestational diabetes
  2. Highly uncontrolled diabetes (HbA1c ≥ 11.0%)
  3. Excessive alcohol intake (210 g and 140 g/week for men and women, respectively) within the previous 2 years
  4. A history of taking thiazolidinedione or sodium-glucose cotransporter 2 inhibitor class medications within the last 12 weeks, or a history of discontinuing these medications due to severe side effects
  5. Treatment with four or more classes of antidiabetic medications
  6. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma, within 24 weeks
  7. Intake of drugs that can cause steatotic liver disease (amiodarone, methotrexate, tamoxifen, valproate, etc.)
  8. Allergy or hypersensitivity to the study drugs or their constituents
  9. Oral or parenteral chronic corticosteroid therapy (more than 14 consecutive days) that requires continual adjustments in corticosteroid dose for therapeutic purposes within 8 weeks
  10. Galactosemia
  11. Genetic disorders such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
  12. Malignant tumors currently undergoing treatment or progression
  13. A history of substance abuse or alcohol intoxication within 12 weeks
  14. Infection of human immunodeficiency virus
  15. Severe infection
  16. Pre- and post-operative status, or severe trauma
  17. Cardiac failure within 24 weeks (class III to IV in the NYHA classification)
  18. Acute cardiovascular event within 12 weeks (unstable angina, myocardial infarction, transient ischemic attack, cerebrovascular disease, coronary artery bypass grafting, or coronary intervention)
  19. AAcute and chronic renal disease (estimated glomerular filtration rate < 45 mL/min/1.73 m²) or dialysis
  20. Pregnant or lactating women
  21. Individuals whom the investigator determines to be unsuitable for participation in the clinical trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Pioglitazone monotherapy
Pioglitazone 15mg 1T daily for 24 weeks
Drug: Pioglitazone
The investigators will compare the degree of liver fat before and after pioglitazone monotherapy.
Experimental: Pioglitazone + Empagliflozin combination therapy
Pioglitazone 15mg 1T + Empagliflozin 10mg 1T combination daily for 24 weeks
Drug: Combination of pioglitazone and empagliflozin
The investigators will compare the degree of liver fat before and after pioglitazone and empagliflozin combination therapy.
Experimental: Empagliflozin monotherapy
Empagliflozin 10mg 1T daily for 24 weeks
Drug: Empagliflozin
The investigators will compare the degree of liver fat before and after empagliflozin monotherapy.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in liver fat fraction (%) measured by MRI-PDFF in the largest possible polygonal region of interest encompassing both lobes of the liver
Time Frame: After 24 weeks of treatment
To measure the fat fraction, we drew the largest possible polygonal region of interest encompassing both lobes of the liver on a cross-sectional image, while avoiding blood vessels, bile ducts, and distinct hepatic lesions.
After 24 weeks of treatment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Liver fibrosis measured by magnetic resonance elastography
Time Frame: After 24 weeks of treatment
The secondary endpoint is to analyze the changes before and after drug administration for the following items: liver stiffness (kPa) measured by magnetic resonance elastography.
After 24 weeks of treatment
The changes in glucose metabolism
Time Frame: After 24 weeks of treatment
The secondary endpoint is to analyze the changes before and after drug administration for the following items: The changes in glucose metabolism including fasting glucose (mg/dL), HbA1c (%), fasting insulin (μIU/mL), homeostatic model assessment for insulin resistance (mg/dL*μIU/mL), and homeostasis model assessment of β-cell function (%)
After 24 weeks of treatment
The changes in lipid profile
Time Frame: After 24 weeks of treatment
The secondary endpoint is to analyze the changes before and after drug administration for the following items: The changes in lipid profile including total cholesterol (mg/dL), triglyceride (mg/dL), high-density lipoprotein-cholesterol (mg/dL), low-density lipoprotein-cholesterol (mg/dL), and free fatty acid (μEq/L).
After 24 weeks of treatment
The changes in liver enzyme
Time Frame: After 24 weeks of treatment
he secondary endpoint is to analyze the changes before and after drug administration for the following items: The changes in liver enzyme including aspartate aminotransferase (IU/L), alanine aminotransferase (IU/L), alkaline phosphatase (IU/L), and gamma-glutamyl transferase (IU/L).
After 24 weeks of treatment
The changes in cytokines
Time Frame: After 24 weeks of treatment
The secondary endpoint is to analyze the changes before and after drug administration for the following items: The changes in cytokines including high sensitivity C-reactive protein (mg/L), adiponectin (μg/mL), and leptin (ng/mL).
After 24 weeks of treatment
The changes in other biochemical parameters
Time Frame: After 24 weeks of treatment
The secondary endpoint is to analyze the changes before and after drug administration for the following items: The changes in other biochemical parameters including complete blood count, platelet count (10³/μL), total protein (g/dL), albumin (g/dL), total bilirubin (mg/dL), blood urea nitrogen (mg/dL), creatinine (mg/dL), and uric acid (mg/dL).
After 24 weeks of treatment
The changes in blood pressure and anthropometric parameters
Time Frame: After 24 weeks of treatment
The secondary endpoint is to analyze the changes before and after drug administration for the following items: The changes in blood pressure and anthropometric parameters including systolic and diastolic blood pressure (mmHg), body weight (kg), body mass index (kg/m², defined as weight [kg] divided by the square of the body height [m]), and waist circumference (cm).
After 24 weeks of treatment
The changes in body composition
Time Frame: After 24 weeks of treatment

The secondary endpoint is to analyze the changes before and after drug administration for the following items: The changes in body composition including abdominal subcutaneous fat area (cm²) and abdominal visceral fat area (cm²).

To measure the body composition, abdominal fat content was assessed using a 3-mm thick cross-sectional abdominal fat CT scan at the midpoint of the L3 vertebra, with the participants in a supine position.
After 24 weeks of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Yonsei University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 6, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 16, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 16, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 10, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 22, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 24, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 3, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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