Pioglitazone and Empagliflozin for Fatty Liver Disease in Type 2 Diabetes

Launched by SEOUL NATIONAL UNIVERSITY BUNDANG HOSPITAL · May 22, 2025

Keywords

ClinConnect Summary

This clinical trial is exploring the effects of two medications, pioglitazone and empagliflozin, taken together to see if they can improve liver health in adults with type 2 diabetes and a condition called metabolic dysfunction-associated fatty liver disease (MAFLD). Each medication has shown benefits on its own, but researchers want to find out if using them together can provide even better results, such as reducing fat in the liver and decreasing inflammation.

To be eligible for this study, participants should be at least 20 years old and have poorly controlled type 2 diabetes, meaning their blood sugar levels are higher than ideal. They should also have signs of fat in the liver and at least one other metabolic issue, like high blood pressure or elevated cholesterol levels. Participants can expect to receive either one or both of the study medications and will be monitored closely throughout the trial. It's important to note that certain individuals, such as those on specific diabetes medications or with other serious health conditions, may not qualify for this study. Overall, this trial could lead to new treatment options for people dealing with both diabetes and fatty liver disease.

Gender

ALL

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.