Pioglitazone and Empagliflozin for Fatty Liver Disease in Type 2 Diabetes

May 22, 2025 updated by: Soo Lim, Seoul National University Bundang Hospital

Evaluation of Pioglitazone and Empagliflozin Combination Therapy in Type 2 Diabetes Patients With Metabolic Dysfunction-Associated Fatty Liver Disease

This exploratory study will assess the efficacy of combined pioglitazone and empagliflozin therapy in improving hepatic and metabolic outcomes in patients with type 2 diabetes mellitus and metabolic dysfunction-associated fatty liver disease (MAFLD). Although each agent has shown beneficial effects individually, evidence on their combined impact on liver health is scarce. This study seeks to determine whether the combination therapy yields additive improvements in hepatic steatosis, inflammation, and fibrosis, potentially offering a new therapeutic strategy for diabetic patients with fatty liver disease.

Study Overview

Status

Status

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

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 (Estimated)

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.
120

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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Soo Lim Dr, MD PhD
  • Phone Number: +82-31-787-7035
  • Email: limsoo@snu.ac.kr

Study Contact Backup

Study Locations

  • Korea, Republic of
      • Seongnam-si, Korea, Republic of
        • Recruiting
        • Seoul National University Bundang Hospital
        • Contact:

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Adults aged 20 years or older.

  2. Patients with inadequately controlled type 2 diabetes mellitus, defined as HbA1c between 7% and 10%, who are currently treated with either:

    • Combination therapy of metformin and a sulfonylurea, or
    • Combination therapy of metformin and a DPP-4 inhibitor, or
    • Metformin monotherapy, or
    • Triple therapy (including metformin) provided that sulfonylurea will be discontinued upon study enrollment.
  3. Evidence of hepatic steatosis within the past 3 months, confirmed by Fibroscan with a controlled attenuation parameter (CAP) ≥ 268 dB/m (consistent with S2 or greater [≥10% hepatocyte steatosis] according to the 2024 EASL-EASD-EASO guidelines).

  4. Presence of at least one of the following metabolic abnormalities:

    • Waist circumference ≥90 cm for men or ≥85 cm for women.
    • Blood pressure ≥130 mmHg systolic or ≥85 mmHg diastolic, or use of antihypertensive medication.
    • Serum triglycerides ≥150 mg/dL or current use of lipid-lowering agents.
    • HDL-cholesterol ≤45 mg/dL for men or ≤50 mg/dL for women.
    • HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) ≥2.5.
    • Serum C-reactive protein (CRP) ≥2 mg/L.
  5. No changes in anti-diabetic or metabolic medications within the past 3 months, unless the changes are deemed by the investigator not to affect study outcomes.

Exclusion Criteria:

  1. Patients receiving insulin therapy or diagnosed with type 1 diabetes mellitus.
  2. Use of the following medications within the past 3 months: GLP-1 receptor agonists, SGLT2 inhibitors, rosiglitazone (TZD), vitamin E, or ursodeoxycholic acid (UDCA).
  3. Presence of secondary causes of hepatic steatosis unrelated to metabolic dysfunction, such as hepatitis B, hepatitis C, or alcoholic fatty liver disease.
  4. Use of medications known to induce hepatic steatosis, including valproic acid, estrogen, tamoxifen, amiodarone, or chloroquine.

  5. Severe organ failure, defined as:

    • Liver failure: AST or ALT > 5 times the upper normal limit (UNL), serum albumin < 3.2 g/dL, platelet count < 60,000/µL, or Child-Pugh-Turcotte stage B or C.
    • Renal failure: Serum creatinine ≥ 2.0 mg/dL, estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m² (CKD-EPI formula), or patients with end-stage renal disease or on dialysis.
  6. Presence of hepatocellular carcinoma, active malignancy, or metastatic cancer.
  7. History of or active bladder cancer.
  8. History of heart failure or current diagnosis of heart failure.
  9. Presence of terminal illnesses.
  10. History of gallstone disease, chronic pancreatitis, or acute pancreatitis.
  11. Underweight patients (body mass index [BMI] < 18.5 kg/m²).
  12. Pregnant women or women planning to become pregnant.
  13. Known hypersensitivity to the active ingredients or excipients of the study medications.
  14. History of diabetic ketoacidosis.

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: Double

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
Pioglitazone 15mg
Drug: Empagliflozin 10 MG [Jardiance]
Participants will receive empagliflozin 10 mg, administered orally once daily. The tablet may be taken with or without food.
Experimental: Empagliflozin
Empagliflozin 10mg
Drug: Pioglitazone 15 MG [Actos]
Participants will receive pioglitazone 15 mg, administered orally once daily. The tablet may be taken with or without food.
Experimental: Pioglitazone & Empagliflozin
Pioglitazone 15mg + Empagliflozin 10mg
Drug: Empagliflozin 10 MG [Jardiance] + Pioglitazone 15 MG [Actos]
Participants will receive one tablet of pioglitazone 15 mg and one tablet of empagliflozin 10 mg, administered orally once daily. Both tablets may be taken with or without food.

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
Proportion of Participants Achieving HbA1c Treatment Targets
Time Frame: 24 weeks
Percentage of participants who achieve the predefined HbA1c treatment goal at 24 weeks.
24 weeks
Change in Fibroscan Controlled Attenuation Parameter (CAP) Score
Time Frame: 24 weeks
Assessment of changes in hepatic steatosis as measured by the controlled attenuation parameter (CAP) score using Fibroscan technology over a 24-week period.
24 weeks

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
Change in HbA1c Levels
Time Frame: 24 weeks
Change in glycated hemoglobin (HbA1c) from baseline after 24 weeks of treatment.
24 weeks
Change in Liver Stiffness Measurement
Time Frame: 24 weeks
Change in liver stiffness measurement (LSM) assessed using Fibroscan
24 weeks
Change in Non-Invasive Blood-Based Fibrosis Markers
Time Frame: 12 weeks, 24 weeks
Change in NAFLD score, Fibrosis-4 (FIB-4) index, and AST to Platelet Ratio Index (APRI) over 12 and 24 weeks.
12 weeks, 24 weeks
Change in Anthropometric Measures
Time Frame: 12 weeks, 24 weeks
Changes in metabolic parameters including body weight, body mass index (BMI), waist circumference
12 weeks, 24 weeks
Change in Lipid Parameters
Time Frame: 12 weeks, 24 weeks
Changes in blood lipid profile (total cholesterol, LDL-c, HDL-c, triglycerides)
12 weeks, 24 weeks
Change in Liver Function Tests
Time Frame: 12 weeks, 24 weeks
Change in liver function markers including AST, ALT, gamma-glutamyl transferase (gamma-GT), albumin, bilirubin, and prothrombin time
12 weeks, 24 weeks
Change in Fibrosis Biomarker
Time Frame: 12 weeks, 24 weeks
Change in serum type IV collagen levels
12 weeks, 24 weeks
Change in Inflammatory Biomarker
Time Frame: 12 weeks, 24 weeks
Change in high-sensitivity C-reactive protein (hs-CRP) levels
12 weeks, 24 weeks

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Other Blood Biomarkers
Time Frame: 24 weeks
Change in ketone body levels
24 weeks
Change in Proteinuria
Time Frame: 24 weeks
Change in urinary albumin-to-creatinine ratio, protein-to-creatinine ratio
24 weeks

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.
Seoul National University Bundang Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Celltrion

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.
January 1, 2025

Primary Completion (Estimated)

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.
December 31, 2026

Study Completion (Estimated)

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 30, 2027

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).
April 29, 2025

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.
May 22, 2025

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.
May 25, 2025

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.
May 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.
May 22, 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.
May 1, 2025

More Information

Terms related to this study

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.
  • B-2407-911-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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