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Completed

NCT Number: NCT03646292

Antidiabetic Drugs for Steatotic Liver Disease

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.

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Key information

Conditions

MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease Diabetes Mellitus Diabetes Mellitus, Type 2 Digestive System Disease Digestive System Diseases Empagliflozin Endocrine System Diseases Fatty Liver Glucose Metabolism Disorders Hypoglycemic Agents Liver Diseases Metabolic Diseases Metabolic Dysfunction-Associated Steatotic Liver Disease Molecular Mechanisms of Pharmacological Action Non-Alcoholic Fatty Liver Disease Nutritional and Metabolic Diseases Physiological Effects of Drugs Pioglitazone Sodium-Glucose Cotransporter 2 Inhibitors Thiazolidinediones Type 2 Diabetes

Age range

19 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

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

Seoul, 03722, South Korea

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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
  • 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

Treatment and study plan

pioglitazone

Drug

The investigators will compare the degree of liver fat before and after pioglitazone monotherapy.

Empagliflozin

Drug

The investigators will compare the degree of liver fat before and after empagliflozin monotherapy.

Combination of pioglitazone and empagliflozin

Drug

The investigators will compare the degree of liver fat before and after pioglitazone and empagliflozin combination therapy.

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

  2. 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).

  3. 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).

  4. 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 (%)

  5. 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).

  6. 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).

  7. 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).

  8. 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.

Sponsors and collaborators

Lead sponsor

Yonsei University

Other

Registry information

Official study 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

Important dates

Study start
2018
Primary completion
2022
Study completion
2022
First posted
Aug 24, 2018
Registry last updated
Mar 5, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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