Pioglitazone and Empagliflozin for Fatty Liver Disease in Type 2 Diabetes

NCT06989723 | Recruiting Phase 4 DMC

• 1 other identifier: B-2407-911-001
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

This exploratory study will assess the efficacy of combined pioglitazone and empagliflozin therapy in improving hepatic and metabolic outcomes in patients with type 2 diabetes mellitus and metabolic dysfunction-associated fatty liver disease (MAFLD). Although each agent has shown beneficial effects individually, evidence on their combined impact on liver health is scarce. This study seeks to determine whether the combination therapy yields additive improvements in hepatic steatosis, inflammation, and fibrosis, potentially offering a new therapeutic strategy for diabetic patients with fatty liver disease.

Conditions

Type 2 Diabetes; Fatty Liver

Outcome Measures

Primary Outcomes (2)

• Proportion of Participants Achieving HbA1c Treatment Targets

  Percentage of participants who achieve the predefined HbA1c treatment goal at 24 weeks.

  24 weeks

• Change in Fibroscan Controlled Attenuation Parameter (CAP) Score

  Assessment of changes in hepatic steatosis as measured by the controlled attenuation parameter (CAP) score using Fibroscan technology over a 24-week period.

  24 weeks

Secondary Outcomes (8)

• Change in HbA1c Levels

  24 weeks

• Change in Liver Stiffness Measurement

  24 weeks

• Change in Non-Invasive Blood-Based Fibrosis Markers

  12 weeks, 24 weeks

• Change in Anthropometric Measures

  12 weeks, 24 weeks

• Change in Lipid Parameters

  12 weeks, 24 weeks

Other Outcomes (2)

• Change in Other Blood Biomarkers

  24 weeks

• Change in Proteinuria

  24 weeks

Study Arms (3)

Pioglitazone

EXPERIMENTAL

Pioglitazone 15mg

Drug: Empagliflozin 10 MG [Jardiance]

Empagliflozin

EXPERIMENTAL

Empagliflozin 10mg

Drug: Pioglitazone 15 MG [Actos]

Pioglitazone & Empagliflozin

EXPERIMENTAL

Pioglitazone 15mg + Empagliflozin 10mg

Drug: Empagliflozin 10 MG [Jardiance] + Pioglitazone 15 MG [Actos]

Interventions

Pioglitazone 15 MG [Actos] DRUG

Participants will receive pioglitazone 15 mg, administered orally once daily. The tablet may be taken with or without food.

Empagliflozin

Empagliflozin 10 MG [Jardiance] DRUG

Participants will receive empagliflozin 10 mg, administered orally once daily. The tablet may be taken with or without food.

Pioglitazone

Empagliflozin 10 MG [Jardiance] + Pioglitazone 15 MG [Actos] DRUG

Participants will receive one tablet of pioglitazone 15 mg and one tablet of empagliflozin 10 mg, administered orally once daily. Both tablets may be taken with or without food.

Pioglitazone & Empagliflozin

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 20 years or older.
• Patients with inadequately controlled type 2 diabetes mellitus, defined as HbA1c between 7% and 10%, who are currently treated with either:
• Combination therapy of metformin and a sulfonylurea, or
• Combination therapy of metformin and a DPP-4 inhibitor, or
• Metformin monotherapy, or
• Triple therapy (including metformin) provided that sulfonylurea will be discontinued upon study enrollment.
• Evidence of hepatic steatosis within the past 3 months, confirmed by Fibroscan with a controlled attenuation parameter (CAP) ≥ 268 dB/m (consistent with S2 or greater \[≥10% hepatocyte steatosis\] according to the 2024 EASL-EASD-EASO guidelines).
• Presence of at least one of the following metabolic abnormalities:
• Waist circumference ≥90 cm for men or ≥85 cm for women.
• Blood pressure ≥130 mmHg systolic or ≥85 mmHg diastolic, or use of antihypertensive medication.
• Serum triglycerides ≥150 mg/dL or current use of lipid-lowering agents.
• HDL-cholesterol ≤45 mg/dL for men or ≤50 mg/dL for women.
• HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) ≥2.5.
• Serum C-reactive protein (CRP) ≥2 mg/L.
• No changes in anti-diabetic or metabolic medications within the past 3 months, unless the changes are deemed by the investigator not to affect study outcomes.

You may not qualify if:

• Patients receiving insulin therapy or diagnosed with type 1 diabetes mellitus.
• Use of the following medications within the past 3 months: GLP-1 receptor agonists, SGLT2 inhibitors, rosiglitazone (TZD), vitamin E, or ursodeoxycholic acid (UDCA).
• Presence of secondary causes of hepatic steatosis unrelated to metabolic dysfunction, such as hepatitis B, hepatitis C, or alcoholic fatty liver disease.
• Use of medications known to induce hepatic steatosis, including valproic acid, estrogen, tamoxifen, amiodarone, or chloroquine.
• Severe organ failure, defined as:
• Liver failure: AST or ALT \> 5 times the upper normal limit (UNL), serum albumin \< 3.2 g/dL, platelet count \< 60,000/µL, or Child-Pugh-Turcotte stage B or C.
• Renal failure: Serum creatinine ≥ 2.0 mg/dL, estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m² (CKD-EPI formula), or patients with end-stage renal disease or on dialysis.
• Presence of hepatocellular carcinoma, active malignancy, or metastatic cancer.
• History of or active bladder cancer.
• History of heart failure or current diagnosis of heart failure.
• Presence of terminal illnesses.
• History of gallstone disease, chronic pancreatitis, or acute pancreatitis.
• Underweight patients (body mass index \[BMI\] \< 18.5 kg/m²).
• Pregnant women or women planning to become pregnant.
• Known hypersensitivity to the active ingredients or excipients of the study medications.

Sponsors & Collaborators

• Seoul National University Bundang Hospital: lead
• Celltrion: collaborator

Study Sites (1)

Seoul National University Bundang Hospital

Seongnam-si, South Korea

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Fatty Liver

Interventions

Pioglitazone; empagliflozin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

Soo Lim Dr, MD PhD

CONTACT

+82-31-787-7035; limsoo@snu.ac.kr

Minji Sohn Dr, PhD

CONTACT

rainbowmjs@naver.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: A randomization sequence will be generated prior to patient enrollment. Patients will be enrolled before the treatment allocation is disclosed. The allocation sequence will be revealed at the time of group assignment, after which the prescribed intervention will be administered. Until group assignment, both the enrolling investigators and the patients who have provided informed consent will remain unaware of the assigned treatment group.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor and Principal Investigator, Division of Endocrinology

Study Record Dates

• First Submitted: April 29, 2025
• First Posted: May 25, 2025
• Study Start: January 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: May 25, 2025

Record last verified: 2025-05

Locations

KR (1)