Status:

RECRUITING

Pioglitazone and Empagliflozin for Fatty Liver Disease in Type 2 Diabetes

Lead Sponsor:

Seoul National University Bundang Hospital

Collaborating Sponsors:

Celltrion

Conditions:

Type 2 Diabetes

Fatty Liver

Eligibility:

All Genders

20+ years

Phase:

PHASE4

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 d...

Eligibility Criteria

Inclusion

  • 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.

Exclusion

  • 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.
  • History of diabetic ketoacidosis.

Key Trial Info

Start Date :

January 1 2025

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

June 30 2027

Estimated Enrollment :

120 Patients enrolled

Trial Details

Trial ID

NCT06989723

Start Date

January 1 2025

End Date

June 30 2027

Last Update

May 25 2025

Active Locations (1)

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Seoul National University Bundang Hospital

Seongnam-si, South Korea