Effect of Empagliflozin and Dulaglutide on MAFLD in Patients With T2D

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Type 2 Diabetes; Metabolic-associated Fatty Liver Disease
• Intervention / Treatment: Drug: Empagliflozin; Drug: Dulaglutide; Drug: Empagliflozin and Dulaglutide

• Study Type: Interventional
• Enrollment (Anticipated): 135
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Soo Lim, MD, PhD; Phone Number: +82-31-787-7035; Email: limsoo@snu.ac.kr
• Study Contact Backup: Name: Minji Sohn, PhD; Phone Number: +82-31-787-8443; Email: rainbowmjs@naver.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Empagliflozin; Empagliflozin 10mg p.o. once daily (available to control over ~25mg)	Drug: Empagliflozin; Empagliflozin 10 mg p.o. once daily (available to control over ~25mg); Other Names: Jardiance
EXPERIMENTAL: Dulaglutide; Dulaglutide 0.75mg s.c. once weekly (available to control over ~1.5mg)	Drug: Dulaglutide; Dulaglutide 0.75mg s.c. once a week (available to control over ~1.5mg); Other Names: Trulicity
EXPERIMENTAL: Empagliflozin and Dulagludie; Empagliflozin 10mg p.o. once daily and dulaglutide 0.75mg s.c. once weekly	Drug: Empagliflozin and Dulaglutide; Empagliflozin 10 mg p.o. once daily with Dulaglutide 0.75mg s.c. once weekly; Other Names: Jardiance and Trulicity

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of LSM score	Liver stiffness measurement (LSM) score by transient elastography	baseline, week 24
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
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
Changes of lipid levels	Cholesterol level will be measured at all visit days	baseline, week 12, week 24
Changes of ketone levels	Ketone level will be measured at all visit days	baseline, week 12, week 24
Changes of liver parenchyma by ultrasonography	improvement or deterioration	baseline, week 24
Changes of liver function parameters	Liver enzymes, albumin will be measured at all visit days.	baseline, week 12, week 24
Changes of liver fibrosis biomarkers	Type IV collagen	baseline, week 24
Changes of inflammation biomarker	high-sensitivity CRP	baseline, week 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of urine markers	Urinalysis will be performed at all visit days	baseline, week 12, week 24
Changes of bone health	parathyroid hormone, 25-hydroxylated vitamin will be measured at all visit days	baseline, week 12, week 24
Changes of gut microbiota	gut microbiota composition, microbiota related to metabolic dysfunction	baseline, week 24

Collaborators and Investigators

• Sponsor: Seoul National University Bundang Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): December 1, 2023
• Primary Completion (ANTICIPATED): June 30, 2024
• Study Completion (ANTICIPATED): December 31, 2025

Study Registration Dates

• First Submitted: April 26, 2021
• First Submitted That Met QC Criteria: November 21, 2021
• First Posted (ACTUAL): December 1, 2021

Study Record Updates

• Last Update Posted (ACTUAL): October 4, 2022
• Last Update Submitted That Met QC Criteria: October 1, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Liver Diseases; Diabetes Mellitus, Type 2; Fatty Liver; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Immunologic Factors; Sodium-Glucose Transporter 2 Inhibitors; Dulaglutide; Immunoglobulin Fc Fragments; Empagliflozin
• Other Study ID Numbers: MAFLD_empa_dula

Drug and device information, study documents

• 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