Antidiabetic Drugs for Steatotic Liver Disease

Yonsei University

Status and phase: Completed; Phase 4

Conditions: Thiazolidinediones; Pioglitazone; Physiological Effects of Drugs; Metabolic Dysfunction-Associated Steatotic Liver Disease; Type 2 Diabetes; Hypoglycemic Agents; Fatty Liver; Molecular Mechanisms of Pharmacological Action; MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease; Sodium-Glucose Cotransporter 2 Inhibitors; Empagliflozin; Digestive System Disease; Non-Alcoholic Fatty Liver Disease; Liver Diseases

Treatments: Drug: Combination of pioglitazone and empagliflozin; Drug: Empagliflozin; Drug: Pioglitazone

Study type: Interventional

Funder types: Other

Identifiers

NCT03646292

4-2018-0655

Details and patient eligibility

About

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.

Enrollment: 51 patients

Sex: All

Ages: 19 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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51 participants in 3 patient groups

Pioglitazone monotherapy

Experimental group

Description:

Pioglitazone 15mg 1T daily for 24 weeks

Treatment:

Drug: Pioglitazone

Empagliflozin monotherapy

Experimental group

Description:

Empagliflozin 10mg 1T daily for 24 weeks

Treatment:

Drug: Empagliflozin

Pioglitazone + Empagliflozin combination therapy

Experimental group

Description:

Pioglitazone 15mg 1T + Empagliflozin 10mg 1T combination daily for 24 weeks

Treatment:

Drug: Combination of pioglitazone and empagliflozin