Metabolic-associated Fatty Liver Disease, Type 2 Diabetes
Conditions
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.
Interventions
DRUGEmpagliflozin
Empagliflozin 10 mg p.o. once daily (available to control over \ 25mg)
DRUGDulaglutide
Dulaglutide 0.75mg s.c. once a week (available to control over \ 1.5mg)
DRUGEmpagliflozin and Dulaglutide
Empagliflozin 10 mg p.o. once daily with Dulaglutide 0.75mg s.c. once weekly
Sponsors
Seoul National University Bundang Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 90 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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 LSM score | baseline, week 24 | Liver stiffness measurement (LSM) score by transient elastography |
| 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 inflammation biomarker | baseline, week 24 | high-sensitivity CRP |
| Changes of lipid levels | baseline, week 12, week 24 | Cholesterol level will be measured at all visit days |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes of gut microbiota | baseline, week 24 | gut microbiota composition, microbiota related to metabolic dysfunction |
| Changes of bone health | baseline, week 12, week 24 | parathyroid hormone, 25-hydroxylated vitamin will be measured at all visit days |
| Changes of urine markers | baseline, week 12, week 24 | Urinalysis will be performed at all visit days |
Contacts
Primary ContactSoo Lim, MD, PhD
Backup ContactMinji Sohn, PhD
Outcome results
None listed