Effect of Empagliflozin and Dulaglutide on MAFLD in Patients With T2D

Phase 4

Not yet recruiting

• Conditions: Metabolic-associated Fatty Liver Disease; Type 2 Diabetes
• Interventions: Drug: Empagliflozin; Drug: Dulaglutide; Drug: Empagliflozin and Dulaglutide

• Registration Number: NCT05140694
• Lead Sponsor: Seoul National University Bundang Hospital

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-04-26
• Study First Submitted QC: 2021-11-21
• Study First Posted: 2021-12-01
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-01
• Last Update Posted: 2022-10-04
• Study Start: 2023-12-01
• Primary Completion: 2024-06-30
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 135

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Empagliflozin	Empagliflozin	Empagliflozin 10mg p.o. once daily (available to control over \~25mg)
Dulaglutide	Dulaglutide	Dulaglutide 0.75mg s.c. once weekly (available to control over \~1.5mg)
Empagliflozin and Dulagludie	Empagliflozin and Dulaglutide	Empagliflozin 10mg p.o. once daily and dulaglutide 0.75mg s.c. once weekly

Primary Outcome Measures

Name	Time	Method
Changes of HbA1c level	baseline, week 12, week 24	Patients achieving the target level
Changes of CAP score	baseline, week 24	Controlled Attenuation Parameter (CAP) score by transient elastography

Secondary Outcome Measures

Name	Time	Method
Changes of LSM score	baseline, week 24	Liver stiffness measurement (LSM) score by transient elastography
Changes of body weight and body composition	baseline, week 24	Body composition by bioelectrical impedance will be measured at baseline and at the end of the study
Changes of lipid levels	baseline, week 12, week 24	Cholesterol level will be measured at all visit days
Changes of ketone levels	baseline, week 12, week 24	Ketone level will be measured at all visit days
Changes of liver parenchyma by ultrasonography	baseline, week 24	improvement or deterioration
Changes of noninvasive liver fibrosis markers	baseline, week 12, week 24	Noninvasive liver fibrosis markers will be calculated at baseline and at the end of the study
Changes of liver function parameters	baseline, week 12, week 24	Liver enzymes, albumin will be measured at all visit days.
Changes of liver fibrosis biomarkers	baseline, week 24	Type IV collagen
Changes of inflammation biomarker	baseline, week 24	high-sensitivity CRP