SGLT2i to Prevent of Liver Complications in Patients With CHB and Diabetes Mellitus

March 16, 2026 updated by: Grace Lai Hung Wong, Chinese University of Hong Kong

Sodium-glucose Co-transporter-2 Inhibitor (SGLT2i) to Prevent of Liver Complications in Patients With Chronic Hepatitis B and Diabetes Mellitus: a Double-blind, Randomised, Placebo-controlled Trial

This is a five-year, double blinded, randomised trial of dapagliflozin versus placebo in patients with chronic hepatitis B and DM or IFG complicated with compensated advanced chronic liver disease (cACLD). 412 subjects will be recruited. Subject will be randomly assigned to receive dapagliflozin 10mg daily or dapagliflozin placebo one tablet daily for up to 5 years. After randomization, subject will be followed up at month 3, month 6 and then 6-monthly until 60 months (follow up ± 4 weeks from scheduled clinic visit is allowed). At each visit, drug compliance, physical examination, observed or reported adverse events will be assessed. 10ml of blood will be taken at each visit and transient elastography to assess fibrosis regression will be performed at 60th month or at withdrawal visit. You are discouraged to use (pegylated)-interferon, any other NA including lamivudine, adefovir, and telbivudine, another SGLT2i Empagliflozin (Jardiance), Dapagliflozin + Metformin XR (Xigduo).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Chronic hepatitis B virus (HBV) infection is a global health problem affecting approximately 234 million people worldwide; of those three-quarter come from the Asia-Pacific region.1 Up to 30%-40% of chronically infected persons will die of liver complications, including liver cancer and cirrhotic complications.2 The Global Burden of Disease Study 2016 revealed HBV as one of the top ten killers worldwide.3 Chronic HBV infection also represents a major global economic burden; with increasing socioeconomic costs.4 Majority of the liver complications and deaths is related to hepatocellular carcinoma (HCC) because of its high incidence rate and unfavourable clinical course.5

Sodium-glucose co-transporter-2 inhibitors (SGLT2i) is a potent antidiabetic agent that lowers blood glucose by inducing renal glycosuria.15 SGLT2i reduces cardiovascular and renal events by marked cardiac anti-fibrotic and anti-inflammatory effects,16 on top of dramatic weight reduction.6 A recent open-label, pilot study of nine patients with biopsy-proven non-alcoholic steatohepatitis (NASH) with type 2 DM received a SGLT2i (empagliflozin) 25 mg daily, for 24 weeks. SGLT2i led to histological improvement in steatosis, ballooning, and fibrosis, compared with historical placebo.7 SGLT2i also leads to more significant reduction of ALT.8 Several other randomised trials and cohort studies supported that SGLT2i also reduces liver fat content and liver fibrosis scores. SGLT2i has additional benefits on liver histology compared to other antidiabetic agents.8 The key pathways include control of hepatic inflammation and fibrosis, improvement of insulin resistance, and reduction of hepatic steatosis. The related mechanisms involve inflammatory parameters like high-sensitivity C-reactive protein, proinflammatory cytokines like interleukin-6 or TNF-alpha, reactive oxygen species and the inhibition of AMPc activation. The improvement was correlated with reductions in body weight, waist circumference and inflammatory parameters. The improvement was not correlated with changes in glucose control.9 All these favourable effects on liver have make it potentially useful to reduce liver complications.

Chronic hepatitis B is major cause of liver complications and death. Antiviral treatment with oral nucleos(t)ide analogues reduces but not abolish the risk of liver complications, especially in those with diabetes mellitus. Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are promising in improving liver outcome in patients with chronic hepatitis B and diabetes mellitus. Our preliminary data provide strong plausibility that SGLT2i reduces the risk of liver complications. We are going to provide the definitive answer to this important clinical question through a randomised trial.

Study Type

Interventional

Enrollment (Estimated)

412

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Patients with chronic hepatitis B on ETV, TDF or TAF monotherapy for at least 12 months.
  2. Known or newly diagnosed type 2 diabetes mellitus (T2D), defined as HbA1c ≥5.7% or fasting blood sugar ≥5.6 mmol/L, or random blood sugar ≥11.1 mmol/L, or 2 hours sugar after oral glucose tolerance test ≥7.8 mmol/L.
  3. Stable use of anti-diabetic drugs in the last three months.
  4. Presence of compensated advanced chronic liver disease (cACLD) with liver stiffness measurement >10.0 kPa, or significant portal hypertension (spleen stiffness measurement > 41.3 kPa), or presence any sign of portal hypertension (e.g. splenomegaly, ascites, varices)
  5. Aged 18 years old or above.
  6. Written informed consent obtained.

Exclusion Criteria:

  1. Patients with hepatitis C virus (HCV) infection as indicated by a positive antibody to HCV (anti-HCV) serology test.
  2. Patients with history of cirrhotic complications or hepatocellular carcinoma
  3. Patients with organ transplantation
  4. Patients receiving a SGLT2i
  5. Contraindications to SGLT2i due to renal insufficiency (GFR < 45 mL/min/1.73m2)
  6. Poor glycaemic control with HbA1c >9.0%
  7. Use of multiple anti-diabetic drugs (3 or more)
  8. Change in anti-diabetic drugs in the last three months.
  9. Serious medical illnesses or malignancy
  10. Age < 18 years
  11. No patient consents

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Dapagliflozin
10mg QD for 60 months
Drug: Dapagliflozin 10mg Tab
Dapagliflozin 10mg Tab QD for 60 months.
Placebo Comparator: Placebo
10mg QD for 60 months
Drug: Placebo 10mg Tab
Placebo 10mg Tab QD for 60 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The primary endpoint is liver complications
Time Frame: 60 months
defined as HCC and any cirrhotic complications, namely ascites, spontaneous bacterial peritonitis (SBP), variceal bleeding, hepatic encephalopathy, and/or hepatorenal syndrome (HRS).
60 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cardiovascular complications
Time Frame: 60 months
defined as cardiovascular deaths, hospitalizations for heart failure, and urgent heart failure
60 months
change in liver stiffness measurement
Time Frame: 60 months
measured with transient elastography Unabbreviated scale title of kPa is kilopascals Minimum 0 kPa Maximum 80 kPa Higher scores mean a worse outcome
60 months
change anthropometric parameters (body weight)
Time Frame: 60 months
body weight
60 months
change anthropometric parameters (waist-hip ratio)
Time Frame: 60 months
waist-hip ratio
60 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chinese University of Hong Kong

Investigators

  • Principal Investigator: Grace LH Wong, MD, Chinese University of Hong Kong

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 26, 2024

Primary Completion (Estimated)

October 31, 2030

Study Completion (Estimated)

March 30, 2031

Study Registration Dates

First Submitted

April 8, 2024

First Submitted That Met QC Criteria

April 12, 2024

First Posted (Actual)

April 15, 2024

Study Record Updates

Last Update Posted (Actual)

March 18, 2026

Last Update Submitted That Met QC Criteria

March 16, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SGLT2i_HBV Study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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