Clinical trial NCT03646292: Antidiabetic Drugs for Steatotic Liver Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease
Type 2 Diabetes
Digestive System Disease
Liver Diseases
Fatty Liver
Metabolic Dysfunction-Associated Steatotic Liver Disease
Non-Alcoholic Fatty Liver Disease
Hypoglycemic Agents
Physiological Effects of Drugs
Sodium-Glucose Cotransporter 2 Inhibitors
Pioglitazone
Molecular Mechanisms of Pharmacological Action
Empagliflozin
Thiazolidinediones
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
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2018-08-24
Enrollment: 51
Sex: ALL
Minimum age (years): 19
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in liver fat fraction (%) measured by MRI-PDFF in the largest possible polygonal region of interest encompassing both lobes of the liver
timeFrame: After 24 weeks of treatment
Secondary outcomes:
measure: Liver fibrosis measured by magnetic resonance elastography
timeFrame: After 24 weeks of treatment
measure: The changes in lipid profile
timeFrame: After 24 weeks of treatment
measure: The changes in liver enzyme
timeFrame: After 24 weeks of treatment
measure: The changes in glucose metabolism
timeFrame: After 24 weeks of treatment
measure: The changes in cytokines
timeFrame: After 24 weeks of treatment
measure: The changes in other biochemical parameters
timeFrame: After 24 weeks of treatment
measure: The changes in blood pressure and anthropometric parameters
timeFrame: After 24 weeks of treatment
measure: The changes in body composition
timeFrame: After 24 weeks of treatment
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea
Study officials:
References: