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
- Conditions
- MASLD - Metabolic Dysfunction-Associated Steatotic Liver DiseaseType 2 DiabetesDigestive System DiseaseLiver DiseasesFatty LiverMetabolic Dysfunction-Associated Steatotic Liver DiseaseNon-Alcoholic Fatty Liver DiseaseHypoglycemic AgentsPhysiological Effects of DrugsSodium-Glucose Cotransporter 2 Inhibitors
- Interventions
- Registration Number
- NCT03646292
- Lead Sponsor
- Yonsei University
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pioglitazone monotherapy Pioglitazone Pioglitazone 15mg 1T daily for 24 weeks Empagliflozin monotherapy Empagliflozin Empagliflozin 10mg 1T daily for 24 weeks Pioglitazone + Empagliflozin combination therapy Combination of pioglitazone and empagliflozin Pioglitazone 15mg 1T + Empagliflozin 10mg 1T combination daily for 24 weeks
- Primary Outcome Measures
Name Time Method Change in liver fat fraction (%) measured by MRI-PDFF in the largest possible polygonal region of interest encompassing both lobes of the liver 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 Outcome Measures
Name Time Method Liver fibrosis measured by magnetic resonance elastography 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.
The changes in lipid profile 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).
The changes in liver enzyme 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).
The changes in glucose metabolism 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 (%)
The changes in cytokines 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).
The changes in other biochemical parameters 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).
The changes in blood pressure and anthropometric parameters 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).
The changes in body composition 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.
Trial Locations
- Locations (1)
Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea
🇰🇷Seoul, Korea, Republic of