Effect of Empagliflozin and Dulaglutide on MAFLD in Patients With T2D

Type 2 Diabetes Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05140694
• Other study ID #: MAFLD_empa_dula
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: December 1, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: October 2022
• Source: Seoul National University Bundang Hospital
• Contact: Soo Lim, MD, PhD
• Phone: +82-31-787-7035
• Email: limsoo[@]snu.ac.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 135
• Est. completion date: December 31, 2025
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Fatty Liver
• Liver Diseases
• Type 2 Diabetes

Intervention

Drug:
• Empagliflozin
Empagliflozin 10 mg p.o. once daily (available to control over ~25mg)
• Dulaglutide
Dulaglutide 0.75mg s.c. once a week (available to control over ~1.5mg)
• Empagliflozin and Dulaglutide
Empagliflozin 10 mg p.o. once daily with Dulaglutide 0.75mg s.c. once weekly

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Bundang Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes of urine markers	Urinalysis will be performed at all visit days	baseline, week 12, week 24
Other	Changes of bone health	parathyroid hormone, 25-hydroxylated vitamin will be measured at all visit days	baseline, week 12, week 24
Other	Changes of gut microbiota	gut microbiota composition, microbiota related to metabolic dysfunction	baseline, week 24
Primary	Changes of HbA1c level	Patients achieving the target level	baseline, week 12, week 24
Primary	Changes of CAP score	Controlled Attenuation Parameter (CAP) score by transient elastography	baseline, week 24
Secondary	Changes of LSM score	Liver stiffness measurement (LSM) score by transient elastography	baseline, week 24
Secondary	Changes of noninvasive liver fibrosis markers	Noninvasive liver fibrosis markers will be calculated at baseline and at the end of the study	baseline, week 12, week 24
Secondary	Changes of body weight and body composition	Body composition by bioelectrical impedance will be measured at baseline and at the end of the study	baseline, week 24
Secondary	Changes of lipid levels	Cholesterol level will be measured at all visit days	baseline, week 12, week 24
Secondary	Changes of ketone levels	Ketone level will be measured at all visit days	baseline, week 12, week 24
Secondary	Changes of liver parenchyma by ultrasonography	improvement or deterioration	baseline, week 24
Secondary	Changes of liver function parameters	Liver enzymes, albumin will be measured at all visit days.	baseline, week 12, week 24
Secondary	Changes of liver fibrosis biomarkers	Type IV collagen	baseline, week 24
Secondary	Changes of inflammation biomarker	high-sensitivity CRP	baseline, week 24