Clinical trial NCT05140694: 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
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Metabolic-associated Fatty Liver Disease
Type 2 Diabetes
Lead sponsor: Seoul National University Bundang Hospital
Sponsor class: OTHER
First posted: 2021-12-01
Enrollment: 135
Sex: ALL
Minimum age (years): 20
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Changes of HbA1c level
timeFrame: baseline, week 12, week 24
measure: Changes of CAP score
timeFrame: baseline, week 24
Secondary outcomes:
measure: Changes of LSM score
timeFrame: baseline, week 24
measure: Changes of noninvasive liver fibrosis markers
timeFrame: baseline, week 12, week 24
measure: Changes of body weight and body composition
timeFrame: baseline, week 24
measure: Changes of lipid levels
timeFrame: baseline, week 12, week 24
measure: Changes of ketone levels
timeFrame: baseline, week 12, week 24
measure: Changes of liver parenchyma by ultrasonography
timeFrame: baseline, week 24
measure: Changes of liver function parameters
timeFrame: baseline, week 12, week 24
measure: Changes of liver fibrosis biomarkers
timeFrame: baseline, week 24
measure: Changes of inflammation biomarker
timeFrame: baseline, week 24
Other outcomes:
measure: Changes of urine markers
timeFrame: baseline, week 12, week 24
measure: Changes of bone health
timeFrame: baseline, week 12, week 24
measure: Changes of gut microbiota
timeFrame: baseline, week 24
Locations:
Study officials:
affiliation: Seoul National University Bundang Hospital
name: Soo Lim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: