Pioglitazone and Empagliflozin for Fatty Liver Disease in Type 2 Diabetes

Phase 4

Recruiting

• Conditions: Type 2 Diabetes; Fatty Liver
• Interventions: Drug: Empagliflozin 10 MG [Jardiance]; Drug: Pioglitazone 15 MG [Actos]; Drug: Empagliflozin 10 MG [Jardiance] + Pioglitazone 15 MG [Actos]

• Registration Number: NCT06989723
• Lead Sponsor: Seoul National University Bundang Hospital

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2025-01-01
• Study First Submitted: 2025-04-29
• Status Verified: 2025-05
• Study First Submitted QC: 2025-05-22
• Last Update Submitted: 2025-05-22
• Study First Posted: 2025-05-25
• Last Update Posted: 2025-05-25
• Primary Completion: 2026-12-31
• Study Completion: 2027-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1. Adults aged 20 years or older.

2. 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.

3. 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).

4. 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.

5. 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.

Exclusion Criteria

1. Patients receiving insulin therapy or diagnosed with type 1 diabetes mellitus.

2. Use of the following medications within the past 3 months: GLP-1 receptor agonists, SGLT2 inhibitors, rosiglitazone (TZD), vitamin E, or ursodeoxycholic acid (UDCA).

3. Presence of secondary causes of hepatic steatosis unrelated to metabolic dysfunction, such as hepatitis B, hepatitis C, or alcoholic fatty liver disease.

4. Use of medications known to induce hepatic steatosis, including valproic acid, estrogen, tamoxifen, amiodarone, or chloroquine.

5. 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.

6. Presence of hepatocellular carcinoma, active malignancy, or metastatic cancer.

7. History of or active bladder cancer.

8. History of heart failure or current diagnosis of heart failure.

9. Presence of terminal illnesses.

10. History of gallstone disease, chronic pancreatitis, or acute pancreatitis.

11. Underweight patients (body mass index [BMI] < 18.5 kg/m²).

12. Pregnant women or women planning to become pregnant.

13. Known hypersensitivity to the active ingredients or excipients of the study medications.

14. History of diabetic ketoacidosis.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pioglitazone	Empagliflozin 10 MG [Jardiance]	Pioglitazone 15mg
Empagliflozin	Pioglitazone 15 MG [Actos]	Empagliflozin 10mg
Pioglitazone & Empagliflozin	Empagliflozin 10 MG [Jardiance] + Pioglitazone 15 MG [Actos]	Pioglitazone 15mg + Empagliflozin 10mg

Primary Outcome Measures

Name	Time	Method
Change in Fibroscan Controlled Attenuation Parameter (CAP) Score	24 weeks	Assessment of changes in hepatic steatosis as measured by the controlled attenuation parameter (CAP) score using Fibroscan technology over a 24-week period.
Proportion of Participants Achieving HbA1c Treatment Targets	24 weeks	Percentage of participants who achieve the predefined HbA1c treatment goal at 24 weeks.

Secondary Outcome Measures

Name	Time	Method
Change in HbA1c Levels	24 weeks	Change in glycated hemoglobin (HbA1c) from baseline after 24 weeks of treatment.
Change in Liver Stiffness Measurement	24 weeks	Change in liver stiffness measurement (LSM) assessed using Fibroscan
Change in Non-Invasive Blood-Based Fibrosis Markers	12 weeks, 24 weeks	Change in NAFLD score, Fibrosis-4 (FIB-4) index, and AST to Platelet Ratio Index (APRI) over 12 and 24 weeks.
Change in Anthropometric Measures	12 weeks, 24 weeks	Changes in metabolic parameters including body weight, body mass index (BMI), waist circumference
Change in Lipid Parameters	12 weeks, 24 weeks	Changes in blood lipid profile (total cholesterol, LDL-c, HDL-c, triglycerides)
Change in Liver Function Tests	12 weeks, 24 weeks	Change in liver function markers including AST, ALT, gamma-glutamyl transferase (gamma-GT), albumin, bilirubin, and prothrombin time
Change in Fibrosis Biomarker	12 weeks, 24 weeks	Change in serum type IV collagen levels
Change in Inflammatory Biomarker	12 weeks, 24 weeks	Change in high-sensitivity C-reactive protein (hs-CRP) levels

Trial Locations

Locations (1)

Seoul National University Bundang Hospital; 🇰🇷 Seongnam-si, Korea, Republic of