Back to resultsEffect of Empagliflozin and Dulaglutide on MAFLD in Patients With T2D
Primary Purpose
Metabolic-associated Fatty Liver Disease, Type 2 Diabetes
Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Empagliflozin
Dulaglutide
Empagliflozin and Dulaglutide
Sponsored by
About this trial
This is an interventional treatment trial for Metabolic-associated Fatty Liver Disease
Eligibility Criteria
Inclusion Criteria:
- age 20 or over
- uncontrolled HbA1c (7~10%) with metformin and/or sulfonylurea
- Hepatic steatosis estimated by Fibroscan (CAP ≥258 dB/m)
MAFLD: presence of any conditions
- Overweight or obese: BMI ≥23 kg/m2 (Asian)
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:
- Significant alcohol consumption
- 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
- Type 1 diabetes mellitus
- medication usage within 3 months: vitamin E, PUFA, UDCA, fish oil, SGLT2 inhibitors, GLP1-RAs, TZDs
Severe organ dysfunction
- liver damage: AST/ALT >x5 UNL, albumin <3.2, platelet <60k, Child-Pugh-Turcotte stage B or C
- kidney damage: serum creatinine ≥2.0 mg/dL or eGFR <50 mL/min/1.72m2
- Hepatocellular carcinoma, active tumor, or metastasis
- End-stage liver disease
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Empagliflozin
Dulaglutide
Empagliflozin and Dulagludie
Arm Description
Empagliflozin 10mg p.o. once daily (available to control over ~25mg)
Dulaglutide 0.75mg s.c. once weekly (available to control over ~1.5mg)
Empagliflozin 10mg p.o. once daily and dulaglutide 0.75mg s.c. once weekly
Outcomes
Primary Outcome Measures
Changes of HbA1c level
Patients achieving the target level
Changes of CAP score
Controlled Attenuation Parameter (CAP) score by transient elastography
Secondary Outcome Measures
Changes of LSM score
Liver stiffness measurement (LSM) score by transient elastography
Changes of noninvasive liver fibrosis markers
Noninvasive liver fibrosis markers will be calculated at baseline and at the end of the study
Changes of body weight and body composition
Body composition by bioelectrical impedance will be measured at baseline and at the end of the study
Changes of lipid levels
Cholesterol level will be measured at all visit days
Changes of ketone levels
Ketone level will be measured at all visit days
Changes of liver parenchyma by ultrasonography
improvement or deterioration
Changes of liver function parameters
Liver enzymes, albumin will be measured at all visit days.
Changes of liver fibrosis biomarkers
Type IV collagen
Changes of inflammation biomarker
high-sensitivity CRP
Full Information
NCT ID
NCT05140694
First Posted
April 26, 2021
Last Updated
October 1, 2022
Sponsor
Seoul National University Bundang Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05140694
Brief Title
Effect of Empagliflozin and Dulaglutide on MAFLD in Patients With T2D
Official Title
A Randomized, Active-comparator Controlled, Parallel-group Study, to Evaluate the Effect of Empagliflozin and Dulaglutide on MAFLD in Patients With Type 2 Diabetes Mellitus
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 1, 2023 (Anticipated)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Seoul National University Bundang Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metabolic-associated Fatty Liver Disease, Type 2 Diabetes
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
InvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
135 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Empagliflozin
Arm Type
Experimental
Arm Description
Empagliflozin 10mg p.o. once daily (available to control over ~25mg)
Arm Title
Dulaglutide
Arm Type
Experimental
Arm Description
Dulaglutide 0.75mg s.c. once weekly (available to control over ~1.5mg)
Arm Title
Empagliflozin and Dulagludie
Arm Type
Experimental
Arm Description
Empagliflozin 10mg p.o. once daily and dulaglutide 0.75mg s.c. once weekly
Intervention Type
Drug
Intervention Name(s)
Empagliflozin
Other Intervention Name(s)
Jardiance
Intervention Description
Empagliflozin 10 mg p.o. once daily (available to control over ~25mg)
Intervention Type
Drug
Intervention Name(s)
Dulaglutide
Other Intervention Name(s)
Trulicity
Intervention Description
Dulaglutide 0.75mg s.c. once a week (available to control over ~1.5mg)
Intervention Type
Drug
Intervention Name(s)
Empagliflozin and Dulaglutide
Other Intervention Name(s)
Jardiance and Trulicity
Intervention Description
Empagliflozin 10 mg p.o. once daily with Dulaglutide 0.75mg s.c. once weekly
Primary Outcome Measure Information:
Title
Changes of HbA1c level
Description
Patients achieving the target level
Time Frame
baseline, week 12, week 24
Title
Changes of CAP score
Description
Controlled Attenuation Parameter (CAP) score by transient elastography
Time Frame
baseline, week 24
Secondary Outcome Measure Information:
Title
Changes of LSM score
Description
Liver stiffness measurement (LSM) score by transient elastography
Time Frame
baseline, week 24
Title
Changes of noninvasive liver fibrosis markers
Description
Noninvasive liver fibrosis markers will be calculated at baseline and at the end of the study
Time Frame
baseline, week 12, week 24
Title
Changes of body weight and body composition
Description
Body composition by bioelectrical impedance will be measured at baseline and at the end of the study
Time Frame
baseline, week 24
Title
Changes of lipid levels
Description
Cholesterol level will be measured at all visit days
Time Frame
baseline, week 12, week 24
Title
Changes of ketone levels
Description
Ketone level will be measured at all visit days
Time Frame
baseline, week 12, week 24
Title
Changes of liver parenchyma by ultrasonography
Description
improvement or deterioration
Time Frame
baseline, week 24
Title
Changes of liver function parameters
Description
Liver enzymes, albumin will be measured at all visit days.
Time Frame
baseline, week 12, week 24
Title
Changes of liver fibrosis biomarkers
Description
Type IV collagen
Time Frame
baseline, week 24
Title
Changes of inflammation biomarker
Description
high-sensitivity CRP
Time Frame
baseline, week 24
Other Pre-specified Outcome Measures:
Title
Changes of urine markers
Description
Urinalysis will be performed at all visit days
Time Frame
baseline, week 12, week 24
Title
Changes of bone health
Description
parathyroid hormone, 25-hydroxylated vitamin will be measured at all visit days
Time Frame
baseline, week 12, week 24
Title
Changes of gut microbiota
Description
gut microbiota composition, microbiota related to metabolic dysfunction
Time Frame
baseline, week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
age 20 or over
uncontrolled HbA1c (7~10%) with metformin and/or sulfonylurea
Hepatic steatosis estimated by Fibroscan (CAP ≥258 dB/m)
MAFLD: presence of any conditions
Overweight or obese: BMI ≥23 kg/m2 (Asian)
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:
Significant alcohol consumption
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
Type 1 diabetes mellitus
medication usage within 3 months: vitamin E, PUFA, UDCA, fish oil, SGLT2 inhibitors, GLP1-RAs, TZDs
Severe organ dysfunction
liver damage: AST/ALT >x5 UNL, albumin <3.2, platelet <60k, Child-Pugh-Turcotte stage B or C
kidney damage: serum creatinine ≥2.0 mg/dL or eGFR <50 mL/min/1.72m2
Hepatocellular carcinoma, active tumor, or metastasis
End-stage liver disease
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Soo Lim, MD, PhD
Phone
+82-31-787-7035
Email
limsoo@snu.ac.kr
First Name & Middle Initial & Last Name or Official Title & Degree
Minji Sohn, PhD
Phone
+82-31-787-8443
Email
rainbowmjs@naver.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Soo Lim, MD, PhD
Organizational Affiliation
Seoul National University Bundang Hospital
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Effect of Empagliflozin and Dulaglutide on MAFLD in Patients With T2D
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