MASLD - Metabolic Dysfunction-Associated Steatotic Liver DiseasePhase 4NCT03646292
Antidiabetic Drugs for Steatotic Liver Disease
A Phase 4 study testing Pioglitazone, Empagliflozin and Combination of pioglitazone and empagliflozin in people with MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease and Type 2 Diabetes, run by Yonsei University at 1 site in South Korea.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 19 to 75 years
- Conditions the study is for
- MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease, Type 2 Diabetes, Digestive System Disease
- What is being tested?
- Pioglitazone, Empagliflozin and Combination of pioglitazone and empagliflozin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 1 siteSouth Korea
- Study dates
- 6 Dec 2018to 16 Jun 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women aged 19 to 75 years
- 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
- Individuals diagnosed with steatotic liver disease as documented by abdominal ultrasonography within the previous year
- Individuals who have voluntarily agreed in written form to participate in the clinical trial after hearing the explanation of this clinical trial
- Individuals who understand the content of the clinical trial and are able to participate in the trial until the end of the clinical trial
Who cannot join
- Type 1 diabetes and gestational diabetes
- Highly uncontrolled diabetes (HbA1c ≥ 11.0%)
- Excessive alcohol intake (210 g and 140 g/week for men and women, respectively) within the previous 2 years
- 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
- Treatment with four or more classes of antidiabetic medications
- Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma, within 24 weeks
Show all 21Show fewer
- Intake of drugs that can cause steatotic liver disease (amiodarone, methotrexate, tamoxifen, valproate, etc.)
- Allergy or hypersensitivity to the study drugs or their constituents
- Oral or parenteral chronic corticosteroid therapy (more than 14 consecutive days) that requires continual adjustments in corticosteroid dose for therapeutic purposes within 8 weeks
- Galactosemia
- Genetic disorders such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
- Malignant tumors currently undergoing treatment or progression
- A history of substance abuse or alcohol intoxication within 12 weeks
- Infection of human immunodeficiency virus
- Severe infection
- Pre- and post-operative status, or severe trauma
- Cardiac failure within 24 weeks (class III to IV in the NYHA classification)
- Acute cardiovascular event within 12 weeks (unstable angina, myocardial infarction, transient ischemic attack, cerebrovascular disease, coronary artery bypass grafting, or coronary intervention)
- AAcute and chronic renal disease (estimated glomerular filtration rate < 45 mL/min/1.73 m²) or dialysis
- Pregnant or lactating women
- Individuals whom the investigator determines to be unsuitable for participation in the clinical trial
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea
Seoul, 03722
About this study
Official title: 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.
- Conditions
- MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease, Type 2 Diabetes, Digestive System Disease, Liver Diseases, Fatty Liver, Metabolic Dysfunction-Associated Steatotic Liver Disease
- Being tested
- Pioglitazone, Empagliflozin, Combination of pioglitazone and empagliflozin
- Keywords
- Non-alcoholic Fatty Liver Disease, Hypoglycemic Agents, Physiological Effects of Drugs, Sodium-Glucose Cotransporter 2 Inhibitors, Pioglitazone, Molecular Mechanisms of Pharmacological Action, Empagliflozin, Metabolic Dysfunction-Associated Steatotic Liver Disease, Type 2 Diabetes, Digestive System Disease, Liver Diseases, Fatty Liver, Thiazolidinediones
- Medical subject headings
- Diabetes Mellitus, Type 2, Digestive System Diseases, Liver Diseases, Fatty Liver, Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PioglitazoneDrug
The investigators will compare the degree of liver fat before and after pioglitazone monotherapy.
EmpagliflozinDrug
The investigators will compare the degree of liver fat before and after empagliflozin monotherapy.
Combination of pioglitazone and empagliflozinDrug
The investigators will compare the degree of liver fat before and after pioglitazone and empagliflozin combination therapy.
| Study group | Role | What they receive |
|---|---|---|
| Pioglitazone monotherapy | Experimental | Pioglitazone 15mg 1T daily for 24 weeks Receives: Drug: Pioglitazone |
| Empagliflozin monotherapy | Experimental | Empagliflozin 10mg 1T daily for 24 weeks Receives: Drug: Empagliflozin |
| Pioglitazone + Empagliflozin combination therapy | Experimental | Pioglitazone 15mg 1T + Empagliflozin 10mg 1T combination daily for 24 weeks Receives: Drug: Combination of pioglitazone and empagliflozin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in liver fat fraction (%) measured by MRI-PDFF in the largest possible polygonal region of interest encompassing both lobes of the liver
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.
Measured: After 24 weeks of treatment
Secondary outcomes (8)
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 stiffness (kPa) measured by magnetic resonance elastography.
Measured: After 24 weeks of treatment
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 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).
Measured: After 24 weeks of treatment
The changes in liver enzyme
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).
Measured: After 24 weeks of treatment
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 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 (%)
Measured: After 24 weeks of treatment
The changes in cytokines
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).
Measured: After 24 weeks of treatment
The changes in other biochemical parameters
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).
Measured: After 24 weeks of treatment
The changes in blood pressure and anthropometric parameters
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).
Measured: After 24 weeks of treatment
The changes in body composition
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.
Measured: After 24 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2018
- Study start6 Dec 2018
- Primary completion16 Jun 2022
- Study completion16 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MASLD - Metabolic Dysfunction-Associated Steatotic Liver DiseaseStudies of the same condition, open and under way.
- More trials run by Yonsei UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This study will evaluate the efficacy in lowering liver fat and the safety of empagliflozin 10mg, pioglitazone 15mg, alone or in combination (empagliflozin 10mg/pioglitazone 15mg), over a 24-week period.
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03646292
- Sponsor's protocol ID
- 4-2018-0655
- Status last verified
- Mar 2025
- First submitted
- 10 Aug 2018
- Last updated
- 5 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lee M, Hong S, Cho Y, Rhee H, Yu MH, Bae J, Lee YH, Lee BW, Kang ES, Cha BS. Synergistic benefit of thiazolidinedione and sodium-glucose cotransporter 2 inhibitor for metabolic dysfunction-associated steatotic liver disease in type 2 diabetes: a 24-week, open-label, randomized controlled trial. BMC Med. 2025 May 7;23(1):266. doi: 10.1186/s12916-025-04017-x.
PubMed 40336058
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03646292
- Acronym / sponsor ID
- 4-2018-0655
- Conditions
- MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease, Type 2 Diabetes, Digestive System Disease, Liver Diseases, Fatty Liver, Metabolic Dysfunction-Associated Steatotic Liver Disease
- Keywords
- Non-alcoholic Fatty Liver Disease, Hypoglycemic Agents, Physiological Effects of Drugs, Sodium-Glucose Cotransporter 2 Inhibitors, Pioglitazone, Molecular Mechanisms of Pharmacological Action, Empagliflozin, Metabolic Dysfunction-Associated Steatotic Liver Disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Study start
- 6 Dec 2018 (actual)
- Primary completion
- 16 Jun 2022 (actual)
- Study completion
- 16 Jun 2022 (actual)
- First posted
- 24 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- This study will evaluate the efficacy in lowering liver fat and the safety of empagliflozin 10mg, pioglitazone 15mg, alone or in combination (empagliflozin 10mg/pioglitazone 15mg), over a 24-week period.
| Arm | Type | Receives |
|---|---|---|
| Pioglitazone monotherapy | Experimental | Drug: PioglitazonePioglitazone 15mg 1T daily for 24 weeks |
| Empagliflozin monotherapy | Experimental | Drug: EmpagliflozinEmpagliflozin 10mg 1T daily for 24 weeks |
| Pioglitazone + Empagliflozin combination therapy | Experimental | Drug: Combination of pioglitazone and empagliflozinPioglitazone 15mg 1T + Empagliflozin 10mg 1T combination daily for 24 weeks |
Who may qualify
- Ages
- 19 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Men and women aged 19 to 75 years
- 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
- Individuals diagnosed with steatotic liver disease as documented by abdominal ultrasonography within the previous year
- Individuals who have voluntarily agreed in written form to participate in the clinical trial after hearing the explanation of this clinical trial
- Individuals who understand the content of the clinical trial and are able to participate in the trial until the end of the clinical trial
Key exclusion criteria (21 listed)
- Type 1 diabetes and gestational diabetes
- Highly uncontrolled diabetes (HbA1c ≥ 11.0%)
- Excessive alcohol intake (210 g and 140 g/week for men and women, respectively) within the previous 2 years
- 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
- Treatment with four or more classes of antidiabetic medications
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PioglitazoneThe investigators will compare the degree of liver fat before and after pioglitazone monotherapy. | Drug | Pioglitazone monotherapy |
| EmpagliflozinThe investigators will compare the degree of liver fat before and after empagliflozin monotherapy. | Drug | Empagliflozin monotherapy |
| Combination of pioglitazone and empagliflozinThe investigators will compare the degree of liver fat before and after pioglitazone and empagliflozin combination therapy. | Drug | Pioglitazone + Empagliflozin combination therapy |
Primary outcome
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.
8 secondary outcomes
Liver fibrosis measured by magnetic resonance elastography
Time frame: After 24 weeks of treatment
The changes in lipid profile
Time frame: After 24 weeks of treatment
The changes in liver enzyme
Time frame: After 24 weeks of treatment
The changes in glucose metabolism
Time frame: After 24 weeks of treatment
The changes in cytokines
Time frame: After 24 weeks of treatment
The changes in other biochemical parameters
Time frame: After 24 weeks of treatment
The changes in blood pressure and anthropometric parameters
Time frame: After 24 weeks of treatment
The changes in body composition
Time frame: After 24 weeks of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2025.
- Derived from this study: PubMed 40336058Lee M, Hong S, Cho Y, Rhee H, Yu MH, Bae J, Lee YH, Lee BW, Kang ES, Cha BS. Synergistic benefit of thiazolidinedione and sodium-glucose cotransporter 2 inhibitor for metabolic dysfunction-associated steatotic liver disease in type 2 diabetes: a 24-week, open-label, randomized controlled trial. BMC Med. 2025 May 7;23(1):266. doi: 10.1186/s12916-025-04017-x.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pioglitazone, Empagliflozin and Combination of pioglitazone and empagliflozin in people with MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease and Type 2 Diabetes, run by Yonsei University at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03646292, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2025.