Effect of Empagliflozin and Dulaglutide on MAFLD in Patients With T2D

Seoul National University

Status and phase: Not yet enrolling; Phase 4

Conditions: Metabolic-associated Fatty Liver Disease; Type 2 Diabetes

Treatments: Drug: Empagliflozin; Drug: Empagliflozin and Dulaglutide; Drug: Dulaglutide

Study type: Interventional

Funder types: Other

Identifiers

NCT05140694

MAFLD_empa_dula

Details and patient eligibility

About

The co-administration of SGLT2 inhibitor and GLP-1 receptor agonist would be safe and effective on glycemic control in subjects with type 2 diabetes mellitus and MAFLD better than empagliflozin or dulaglutide alone.

The SGLT2 inhibitor and GLP-1 receptor agonist would be safe and effective on fatty liver disease in subjects with type 2 diabetes mellitus and MAFLD.

Enrollment: 135 estimated patients

Sex: All

Ages: 20 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. age 20 or over

2. uncontrolled HbA1c (7~10%) with metformin and/or sulfonylurea

3. Hepatic steatosis estimated by Fibroscan (CAP ≥258 dB/m)

4. MAFLD: presence of any conditions

   1. Overweight or obese: BMI ≥23 kg/m2 (Asian)

   2. Metabolic dysregulation: at least of two of following criteria

      • Waist circumference: ≥90/80 cm in men and women (Asian)
      • Blood pressure ≥130/85 mmHg or drug treatment
      • Plasma triglycerides ≥150 mg/dL or drug treatment
      • Plasma HDL-cholesterol <40/50 mg/dL for men and women or drug treatment
      • Prediabetes (i.e. fasting glucose levels 100 to 125 mg/dL or 2-hour post-load glucose levels 140 to 199 mg/dL or HbA1c 5.7% to 6.4%
      • HOMA-insulin resistance score ≥2.5
      • Plasma high-sensitivity CRP >2 mg/L

Exclusion criteria

1. Significant alcohol consumption

2. Other competing causes for hepatic steatosis: viral hepatitis, drug-induced hepatitis, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha1 anti-trypsin deficiency, Celiac disease, Overt hypothyroidism, other secondary causes

3. Type 1 diabetes mellitus

4. medication usage within 3 months: vitamin E, PUFA, UDCA, fish oil, SGLT2 inhibitors, GLP1-RAs, TZDs

5. Severe organ dysfunction

   1. liver damage: AST/ALT >x5 UNL, albumin <3.2, platelet <60k, Child-Pugh-Turcotte stage B or C
   2. kidney damage: serum creatinine ≥2.0 mg/dL or eGFR <50 mL/min/1.72m2

6. Hepatocellular carcinoma, active tumor, or metastasis

7. End-stage liver disease

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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135 participants in 3 patient groups

Empagliflozin

Experimental group

Description:

Empagliflozin 10mg p.o. once daily (available to control over \~25mg)

Treatment:

Drug: Empagliflozin

Dulaglutide

Experimental group

Description:

Dulaglutide 0.75mg s.c. once weekly (available to control over \~1.5mg)

Treatment:

Drug: Dulaglutide

Empagliflozin and Dulagludie

Experimental group

Description:

Empagliflozin 10mg p.o. once daily and dulaglutide 0.75mg s.c. once weekly

Treatment:

Drug: Empagliflozin and Dulaglutide