Clinical trial NCT06989723: Pioglitazone and Empagliflozin for Fatty Liver Disease in Type 2 Diabetes
Official title: Evaluation of Pioglitazone and Empagliflozin Combination Therapy in Type 2 Diabetes Patients With Metabolic Dysfunction-Associated Fatty Liver Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Type 2 Diabetes
Fatty Liver
Lead sponsor: Seoul National University Bundang Hospital
Sponsor class: OTHER
Collaborators: name: Celltrion
First posted: 2025-05-25
Enrollment: 120
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of Participants Achieving HbA1c Treatment Targets
timeFrame: 24 weeks
measure: Change in Fibroscan Controlled Attenuation Parameter (CAP) Score
timeFrame: 24 weeks
Secondary outcomes:
measure: Change in HbA1c Levels
timeFrame: 24 weeks
measure: Change in Liver Stiffness Measurement
timeFrame: 24 weeks
measure: Change in Non-Invasive Blood-Based Fibrosis Markers
timeFrame: 12 weeks, 24 weeks
measure: Change in Anthropometric Measures
timeFrame: 12 weeks, 24 weeks
measure: Change in Lipid Parameters
timeFrame: 12 weeks, 24 weeks
measure: Change in Liver Function Tests
timeFrame: 12 weeks, 24 weeks
measure: Change in Fibrosis Biomarker
timeFrame: 12 weeks, 24 weeks
measure: Change in Inflammatory Biomarker
timeFrame: 12 weeks, 24 weeks
Other outcomes:
measure: Change in Other Blood Biomarkers
timeFrame: 24 weeks
measure: Change in Proteinuria
timeFrame: 24 weeks
Locations:
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
Study officials:
References: