NCT04642261

Effect of Empagliflozin on Liver Fat in Non-diabetic Patients

Completed Phase 4 Last updated 7 December 2023

What this trial tests

Phase 4 trial testing Empagliflozin 10 MG in Non-alcoholic Fatty Liver Disease in 98 participants. Completed in 30 June 2023.

Timeline

1 January 2021

Primary endpoint
31 May 2023

30 June 2023

Quick facts

Lead sponsor	The University of Hong Kong
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	98
Start date	1 January 2021
Primary completion	31 May 2023
Estimated completion	30 June 2023
Sites	1 location across Hong Kong

Drugs / interventions tested

• Empagliflozin 10 MG — full drug profile →
• Placebo pills — full drug profile →

Conditions studied

• Non-alcoholic Fatty Liver Disease — all drugs for Non-alcoholic Fatty Liver Disease →

Sponsor

The University of Hong Kong

Who can join

Adults 18 to 80, any sex, with Non-alcoholic Fatty Liver Disease. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own 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 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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Therapeutic management of metabolic dysfunction associated steatotic liver disease.
   Zeng J, Fan JG, Francque SM. · · 2024 · cited 75× · PMID 38193865 · DOI 10.1002/ueg2.12525
2. Antioxidant and anti-inflammatory agents in chronic liver diseases: Molecular mechanisms and therapy.
   Zhang CY, Liu S, Yang M. · · 2023 · cited 45× · PMID 36926234 · DOI 10.4254/wjh.v15.i2.180
3. 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.
   Cheung KS, Ng HY, Hui RWH, Lam LK, et al · · 2024 · cited 30× · PMID 38536017 · DOI 10.1097/hep.0000000000000855
4. Understanding NAFLD: From Case Identification to Interventions, Outcomes, and Future Perspectives.
   Clayton-Chubb D, Kemp W, Majeed A, Lubel JS, et al · · 2023 · cited 26× · PMID 36771394 · DOI 10.3390/nu15030687
5. GLP-1 RAs and SGLT-2 Inhibitors for Insulin Resistance in Nonalcoholic Fatty Liver Disease: Systematic Review and Network Meta-Analysis.
   Yan H, Huang C, Shen X, Li J, et al · · 2022 · cited 24× · PMID 35909522 · DOI 10.3389/fendo.2022.923606
6. Lessons on Drug Development: A Literature Review of Challenges Faced in Nonalcoholic Fatty Liver Disease (NAFLD) Clinical Trials.
   Chen JYS, Chua D, Lim CO, Ho WX, et al · · 2022 · cited 20× · PMID 36613602 · DOI 10.3390/ijms24010158
7. Antifibrotic therapies for metabolic dysfunction-associated steatotic liver disease.
   Schwabe RF, Tacke F, Sugimoto A, Friedman SL. · · 2025 · cited 13× · PMID 40689145 · DOI 10.1016/j.jhepr.2025.101421
8. MAFLD Pandemic: Updates in Pharmacotherapeutic Approach Development.
   Khaznadar F, Khaznadar O, Petrovic A, Hefer M, et al · · 2024 · cited 10× · PMID 39057018 · DOI 10.3390/cimb46070376