Effect of Empagliflozin on Liver Fat in Non-diabetic Patients

NCT04642261 | Completed Phase 4 DMC

• 1 other identifier: UW 20-065
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

Brief Summary

Non-alcoholic fatty liver disease (NAFLD) is a global epidemic with a prevalence of 25%. Currently therapies for NAFLD patients without diabetes mellitus (DM) are limited, and are associated with various adverse side effects. Sodium-glucose cotransporter type-2 (SGLT2) inhibitors can reduce hepatic fat content in patients with DM. However, the role of SGLT2 inhibitors in NAFLD patients without DM has not been investigated. Magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) and liver stiffness measurement (LSM) are non-invasive methods to diagnose hepatic steatosis and fibrosis/cirrhosis, respectively. The investigators propose a double-blind, randomized, placebo-controlled trial to compare the effects of empagliflozin (a type of SLGT2 inhibitors) versus placebo (in a 1:1 ratio) in reducing hepatic fat content as measured by MRI-PDFF in NAFLD patients without DM. A total of 98 adult patients will be randomly sampled from the liver clinic in our local hospital. Empagliflozin 10mg daily will be given to the treatment arm. The placebo pill will be manufactured to be identical in appearance to the study drug. Eligible subjects will be followed up until week 52, and will undergo clinical, anthropometric and laboratory assessments (including liver function test and fasting blood) at baseline, week 6, 12, 26, 40 and 52. They will undergo LSM at baseline, week 26 and 52, and MRI-PDFF at baseline and week 52. The primary outcome will be a difference in change of liver fat content (measured by MRI-PDFF) at week 52 from baseline between the two groups. The study results will determine whether SGLT2 inhibitors can reduce hepatic steatosis in NAFLD patients without DM.

Conditions

Non-alcoholic Fatty Liver Disease

Keywords

NAFLD; NASH; fatty liver; empagliflozin; SGLT2 inhibitors

Outcome Measures

Primary Outcomes (1)

• Change in liver fat content

  Difference in the change of liver fat content between the two groups at week 52 from the baseline as measured by MRI-PDFF

  week 52

Secondary Outcomes (17)

• Remission of steatosis

  week 52

• Change of liver fat content

  week 26 and 52

• Changes of alanine aminotransferase (ALT)

  week 52

• Changes of aspartate aminotransferase (AST)

  week 52

• Changes of alkaline phosphatase (ALP)

  week 52

Study Arms (2)

Empagliflozin group

EXPERIMENTAL

Empagliflozin 10mg daily for 52 weeks

Drug: Empagliflozin 10 MG

Placebo group

PLACEBO COMPARATOR

Placebo pills (identical in appearance to empagliflozin 10mg) daily for 52 weeks

Drug: Placebo pills

Interventions

Empagliflozin 10 MG DRUG

Empagliflozin 10mg daily

Also known as: empagliflozin

Empagliflozin group

Placebo pills DRUG

Identical in appearance to empagliflozin 10mg daily

Placebo group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Potential study subjects will first be screened by transient elastography for the presence of hepatic steatosis (defined as a measurement of controlled attenuation parameter \[CAP\] \>= 248 db/M).
• They will be recruited into study if steatosis is \>= 5% as confirmed by MRI-PDFF

You may not qualify if:

• DM (defined as hemoglobin A1c \[HbA1c\] \>= 6.5% or fasting glucose \>= 7.0 mmol/L)
• alcohol intake \> 20g within past 2 years
• concurrent chronic liver diseases (including chronic viral hepatitis infection, autoimmune hepatitis, Wilson's disease, hemochromatosis, congestive hepatopathy, primary biliary cholangitis, primary sclerosing cholangitis, biliary tract obstruction)
• drug-induced liver disease
• usage of drugs that can lead to hepatic steatosis (e.g. steroids, amiodarone, valproate, methotrexate, tamoxifen)
• decompensated cirrhosis (including ascites, hepatic hydrothorax, variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome)
• history of malignancy including HCC
• recreational substance abuse
• pregnancy
• contraindications to empagliflozin use (estimated glomerular filtration rate \[eGFR\] \<45mL/min/1.73m2 as measured by the MDRD equation, history of recurrent genitourinary tract infections, gangrene, or allergy)
• contraindications to MRI (e.g., claustrophobia, certain cardiac pacemakers, implanted medical devices with ferromagnetic properties).

Sponsors & Collaborators

• The University of Hong Kong: lead
• Food and Health Bureau, Hong Kong: collaborator

Study Sites (1)

The University of Hong Kong/Queen Mary Hospital

Hong Kong, Hong Kong, China, 852, Hong Kong

Location

Related Publications (1)

• Cheung KS, Ng HY, Hui RWH, Lam LK, Mak LY, Ho YC, Tan JT, Chan EW, Seto WK, Yuen MF, Leung WK. Effects of empagliflozin on liver fat in patients with metabolic dysfunction-associated steatotic liver disease without diabetes mellitus: A randomized, double-blind, placebo-controlled trial. Hepatology. 2024 Oct 1;80(4):916-927. doi: 10.1097/HEP.0000000000000855. Epub 2024 Mar 27.

  PMID: 38536017 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Fatty Liver

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Study Officials

• Ka Shing Cheung, MD, MPH

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The placebo pills will be manufactured in identical appearance to the study drug (empagliflozin)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Model Details: Eligible subjects will be randomly allocated to either the empagliflozin group or placebo group (i.e. control group)

Study Record Dates

• First Submitted: November 6, 2020
• First Posted: November 24, 2020
• Study Start: January 1, 2021
• Primary Completion: May 31, 2023
• Study Completion: June 30, 2023
• Last Updated: December 7, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)