Effect of Empagliflozin on Liver Fat in Non-diabetic Patients
Condition: Non-alcoholic Fatty Liver Disease
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      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 are antidiabetic drugs that reduce hepatic fat content in patients with DM, which
      is independent of glycemic control. 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) is an emerging non-invasive imaging technique, and is more sensitive than
      liver biopsy/histology in quantifying liver fat change. Liver stiffness measurement (LSM) by
      transient elastography is a non-invasive method to diagnose fibrosis/cirrhosis with high
      accuracy.

      The novelty of utilizing the concept of "drug repositioning" by changing the role of SGLT2
      inhibitors in treating DM to treating NAFLD in patients without DM deserves exploration. 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 clinical 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 secondary outcomes will be
      remission of steatosis (MRI-PDFF <5%) at week 52, reduction of liver fibrosis (LSM) at week
      26 and 52, improvement of laboratory results (including liver transaminases and ductal
      enzymes, fasting glucose, HbA1c, lipid profile), improvement of anthropometric measurements,
      and combined cardiovascular and cerebrovascular events.

      The study results will determine whether SGLT2 inhibitors can reduce hepatic steatosis and
      regress fibrosis in NAFLD patients without DM.
    

Intervention name(s): Empagliflozin 10 MG; Placebo pills
Intervention type(s): Drug; Drug
Intervention description(s): Empagliflozin 10mg daily; Identical in appearance to empagliflozin 10mg daily
Other intervention name(s): empagliflozin
Intervention MeSH terms: Empagliflozin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Eligible subjects will be randomly allocated to either the empagliflozin group or placebo group (i.e. control group)
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: NAFLD; NASH; fatty liver; empagliflozin; SGLT2 inhibitors