Therapeutic Response of Sodium-glucose Co-transporter Type-2 Inhibitor in Non-diabetic MAFLD Patients: a Pilot Study

The goal of this single arm, prospective study is to test the therapeutic response of oral dapagliflozin (Forxiga) 10 mg/day for 24 weeks in non-diabetic MAFLD patients. The primary outcomes are the improvement of liver inflammation or fibrosis parameters after 24 weeks treatment. The adverse events were also recorded.

Study Overview

• Status: Active, not recruiting
• Conditions: Metabolic Associated Fatty Liver Disease
• Intervention / Treatment: Drug: dapagliflozin (Forxiga)

Detailed Description

This is single-arm, prospective study and 50 non-diabetic MAFLD patients are enrolled consecutively at Taipei Tzu Chi Hospital. The non-diabetic definition is no previous history of diabetes mellitus and HbA1C < 6.5%. Fatty liver was diagnosed by imaging such as liver ultrasound or histologic examination. Metabolic dysfunction was defined as overweight/obese, or more than 2 metabolic abnormalities in lean/normal weight subjects. Inclusion criteria were ALT elevation (>35 U/L in male and >25 U/L in female) or FIB-4 >=1.45. Those with cancer history, systolic blood pressure < 100 mmHg, or eGFR < 30 ml/min/1.73m2, or history of urinary tract infection/genital yeast infection were excluded. They received oral dapagliflozin (Forxiga) 10 mg/day for 24 weeks.

The primary outcomes are the change of liver inflammation marker (serum ALT level)or fibrosis parameters after 24 weeks treatment. The adverse events were also recorded. The severity of liver fibrosis was determined using NAFLD-fibrosis score and ultrasound-based elastography method (ARFI).

Total 6 visits Visit 1 (screening): US, ARFI, body composition measurement, BP, BMI, Waist circumference, body fat (%), AST/ALT, albumin, GGT, Cr, TG, CHO, HDL/LDL, glucose ac, HbA1C, Platelet, insulin, CRP Visit 2 (2 weeks): BP, AST/ALT, Cr Visit 3 (4 weeks): BP, BMI, Waist circumference, body fat (%), AST/ALT, albumin, GGT, Cr, TG, glucose ac, HbA1C, platelet Visit 4 (3 months):BP, BMI, Waist circumference, body fat (%), AST/ALT, albumin, GGT, Cr, TG, glucose ac, HbA1C, platelet Visit 5 (6 months): US, ARFI, body composition measurement, BP, BMI, Waist circumference, body fat (%), AST/ALT, albumin, GGT, Cr, TG, CHO, HDL/LDL, glucose ac, HbA1C, Platelet, insulin, CRP Visit 6 (Month 3 off-therapy): BP, BMI, Waist circumference, body fat (%), AST/ALT, albumin, GGT, Cr, TG, CHO, HDL/LDL, glucose ac, HbA1C, Platelet Record adverse events and number of pills left in each visits

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• Taiwan
  • New Taipei city, Taiwan, 23142
    • Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• MAFLD patients (hepatic steatosis plus metabolic dysfunction
• ALT elevation (>35 U/L in male and >25 U/L in female) or FIB-4 >=1.45

Exclusion Criteria:

1. diabetes history or HbA1C> 6.5
2. cancer history
3. systolic blood pressure < 100 mmHg
4. eGFR < 30 ml/min/1.73m2
5. history of urinary tract infection/genital yeast infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: dapagliflozin (Forxiga) treatment; The participants received oral dapagliflozin (Forxiga) 10 mg/day for 24 weeks	Drug: dapagliflozin (Forxiga); The participants received oral dapagliflozin (Forxiga) 10 mg/day for 24 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of liver inflammatory marker	the change of ALT between baseline and week 24 after treatment	24 weeks
Change of liver fibrosis markers between baseline and week 24 after treatment	The higher NAFLD fibrosis score (NFS), the more severe liver fibrosis (no maximal or minimal levels)	24 weeks

Collaborators and Investigators

• Sponsor: Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2023
• Primary Completion (Estimated): November 30, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: February 19, 2023
• First Submitted That Met QC Criteria: March 13, 2023
• First Posted (Actual): March 24, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 27, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Dapagliflozin
• Other Study ID Numbers: TCRD-TPE-112-11

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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