Antidiabetic Drugs for Steatotic Liver Disease

NCT03646292 | Completed Phase 4

• 1 other identifier: 4-2018-0655
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

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

  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.

  After 24 weeks of treatment

Secondary Outcomes (8)

• Liver fibrosis measured by magnetic resonance elastography

  After 24 weeks of treatment

• The changes in lipid profile

  After 24 weeks of treatment

• The changes in liver enzyme

  After 24 weeks of treatment

• The changes in glucose metabolism

  After 24 weeks of treatment

• The changes in cytokines

  After 24 weeks of treatment

Study Arms (3)

Pioglitazone monotherapy

EXPERIMENTAL

Pioglitazone 15mg 1T daily for 24 weeks

Drug: Pioglitazone

Empagliflozin monotherapy

EXPERIMENTAL

Empagliflozin 10mg 1T daily for 24 weeks

Drug: Empagliflozin

Pioglitazone + Empagliflozin combination therapy

EXPERIMENTAL

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

Drug: Combination of pioglitazone and empagliflozin

Interventions

Pioglitazone DRUG

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

Pioglitazone monotherapy

Empagliflozin DRUG

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

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.

Pioglitazone + Empagliflozin combination therapy

Eligibility Criteria

• Age: 19 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

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

Seoul, 03722, South Korea

Location

Related Publications (1)

• Lee M, Hong S, Cho Y, Rhee H, Yu MH, Bae J, Lee YH, Lee BW, Kang ES, Cha BS. Synergistic benefit of thiazolidinedione and sodium-glucose cotransporter 2 inhibitor for metabolic dysfunction-associated steatotic liver disease in type 2 diabetes: a 24-week, open-label, randomized controlled trial. BMC Med. 2025 May 7;23(1):266. doi: 10.1186/s12916-025-04017-x.

  PMID: 40336058 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease

Interventions

Pioglitazone; empagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: open label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 10, 2018
• First Posted: August 24, 2018
• Study Start: December 6, 2018
• Primary Completion: June 16, 2022
• Study Completion: June 16, 2022
• Last Updated: March 5, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)