Digestive System Disease, Empagliflozin, Fatty Liver, Hypoglycemic Agents, Liver Diseases, MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease, Metabolic Dysfunction-Associated Steatotic Liver Disease, Molecular Mechanisms of Pharmacological Action, Non-Alcoholic Fatty Liver Disease, Physiological Effects of Drugs, Pioglitazone, Sodium-Glucose Cotransporter 2 Inhibitors, Thiazolidinediones, Type 2 Diabetes
Conditions
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
Brief 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 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.
Interventions
DRUGPioglitazone
The investigators will compare the degree of liver fat before and after pioglitazone monotherapy.
DRUGEmpagliflozin
The investigators will compare the degree of liver fat before and after empagliflozin monotherapy.
DRUGCombination of pioglitazone and empagliflozin
The investigators will compare the degree of liver fat before and after pioglitazone and empagliflozin combination therapy.
Sponsors
Yonsei University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
open label
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
19 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 (%) |
| 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 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. |
| 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). |
Countries
South Korea
Outcome results
None listed