Efficacy and Safety of Dapagliflozin in Patients with Non-alcoholic Steatohepatitis

NCT05254626 | Completed Phase 2

• 1 other identifier: CL (3148)
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with non-alcoholic fatty liver disease (NAFLD) are at increased risk of more aggressive liver disease; non-alcoholic steatohepatitis (NASH) and at a higher risk of death from cirrhosis, hepatocellular carcinoma and cardiovascular diseases. NAFLD is spreading as an epidemic in patients with metabolic syndrome. Its components include obesity, type 2 diabetes mellitus (T2DM) and dyslipidemia. The prevalence of NAFLD is likely to increase resulting in tremendous clinical, social and economic burdens. Unfortunately, there is no approved medication to treat patients with NASH-induced advanced fibrosis. Weight management is the first line of NASH treatment even in non-obese patients with at least 7% reduction of patient's weight. However, NASH patients need pharmacological treatment. Sodium glucose co-transporter (SGLT2) inhibitors demonstrated favorable effects on NAFLD without weight gain as an adverse event proposed by pioglitazone used for the same indication. SGLT2 inhibitors are able to reduce fatty liver content, as assessed by different imaging techniques, and improve biological markers of NAFLD, especially serum liver enzymes, in patients with or without T2DM. In addition, there are emerging data to suggest a mechanism beyond the reduction of body weight and hyperglycemia in patients with or without diabetes. This study aims to evaluate the efficacy and safety of SGLT2 inhibitors in NASH patients in comparison to pioglitazone. This is a randomized prospective parallel study, where all patients presented with NASH to the outpatient clinic in the National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt; will be screened for specific inclusion and exclusion criteria. Diabetic and non-diabetic patients will be randomly assigned to receive one of two treatment modalities. The first arm will be the NASH patients receiving dapagliflozin and the second arm will be the NASH patients receiving pioglitazone for 24 weeks. Each group will have an equal number of diabetic and non-diabetic patients. All patients will be assessed for body composition, serum creatinine level, fasting blood glucose level, HbA1C, markers of insulin resistance (HOMA-IR), complete blood count, serum liver function tests, and NAFLD fibrosis score (NAS). Liver biopsy will be performed at baseline and at the end of the study and the total NAS score will be calculated. All patients will be assessed for any adverse drug reactions, and for their adherence by pill count method. Also, quality of life will be assessed for all patients using previously designed and validated questionnaire called Chronic Liver Disease Questionnaire (CLDQ).

Conditions

Non-alcoholic Steatohepatitis

Keywords

Dapagliflozin; SGLT2 inhibitors; NASH; Efficacy; Safety; Liver biopsy; Pioglitazone; Fatty Liver; NAFLD activity score

Outcome Measures

Primary Outcomes (1)

• Histological Features (Liver Biopsy)

  Change from baseline of NAFLD Activity Score (NAS) and other histological features. NAS score will be assessed using the NASH Clinical Research Network (NASH CRN) scoring system. NAS score ranges from 0 to 8 and the higher score towards 8 means worse outcome.

  Baseline and 24th week

Secondary Outcomes (16)

• NAFLD fibrosis score

  Baseline and 24th week

• Fibrosis Index Based on 4 factors

  Baseline and 24th week

• Fibro-controlled attenuated parameter (fibro CAP)

  Baseline and 24th week

• Serum Alanine Transaminase level (ALT)

  Baseline, 12th and 24th week

• Serum Aspartate Aminotransferase level (AST)

  Baseline, 12th and 24th week

Other Outcomes (2)

• Serum creatinine

  Baseline, 3rd, 6th, 12th, 18th and 24th week

• Estimated glomerular filtration rate (eGFR)

  Baseline, 3rd, 6th, 12th, 18th and 24th week

Study Arms (4)

Diabetic Group 1

EXPERIMENTAL

25 diabetic patients will be prescribed on dapagliflozin 10 mg - once daily (OD) - to be taken orally (PO) for 24 weeks

Drug: Dapagliflozin 10Mg Tab

Diabetic Group 2

ACTIVE COMPARATOR

25 diabetic patients will be prescribed on Pioglitazone 30 mg - once daily (OD) - to be taken orally (PO) for 24 weeks

Drug: Pioglitazone 30 mg

Non-diabetic Group 1

EXPERIMENTAL

25 non-diabetic patients will be prescribed on dapagliflozin 10 mg - once daily (OD) - to be taken orally (PO) for 24 weeks.

Drug: Dapagliflozin 10Mg Tab

Non-diabetic Group 2

ACTIVE COMPARATOR

25 non-diabetic patients will be prescribed on Pioglitazone 30 mg - once daily (OD) - to be taken orally (PO) for 24 weeks

Drug: Pioglitazone 30 mg

Interventions

Dapagliflozin 10Mg Tab DRUG

Dapagliflozin 10 mg, administered orally and to be prescribed for diabetic and non-diabetic patients with NASH for 24 weeks; in comparison to pioglitazone.

Diabetic Group 1; Non-diabetic Group 1

Pioglitazone 30 mg DRUG

Pioglitazone 30 mg, administered orally and to be prescribed for diabetic and non-diabetic patients with NASH for 24 weeks; as an active control and standard of care treatment.

Diabetic Group 2; Non-diabetic Group 2

Eligibility Criteria

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

You may qualify if:

• Age range 18-65 years.
• Liver biopsy confirming NASH within 6 months.
• For diabetic patients, the patients should be with stable glycemic control defined as HbA1C \<10%.

You may not qualify if:

• Active viral hepatitis (HBV, HCV).
• Child Pugh B or C cirrhosis.
• Alcohol consumption in the past six months.
• A history of alcoholic liver disease.
• Secondary causes of steatohepatitis.
• Autoimmune hepatitis.
• Celiac disease.
• Hemochromatosis or Wilson's disease.
• Drug induced liver injury (DILI) or patient with history of taking medication(s) that may cause fatty liver (e.g., tamoxifen, valproic acid, amiodarone, methotrexate, steroids, oral contraceptives).
• Obstructive biliary disease.
• Serum alanine aminotransferase (ALT) more than 2.5 folds of UNL.
• History of serious hypersensitivity to dapagliflozin or pioglitazone or any component of the formulation.
• Pregnancy and breastfeeding.
• Renal impairment (eGFR \<45 mL/minute/1.73 m2), end-stage renal disease (ESRD), or patients on dialysis.
• Having any medical condition that would affect metabolism (i.e., known hyperthyroidism or hypothyroidism).

Sponsors & Collaborators

• Cairo University: lead

Study Sites (1)

National Hepatology and Tropical Medicine Research Institute

Cairo, Cairo Governorate, Egypt

Location

Related Publications (1)

• Abdel Monem MS, Adel A, Abbassi MM, Abdelaziz DH, Hassany M, Raziky ME, Sabry NA. Efficacy and safety of dapagliflozin compared to pioglitazone in diabetic and non-diabetic patients with non-alcoholic steatohepatitis: A randomized clinical trial. Clin Res Hepatol Gastroenterol. 2025 Mar;49(3):102543. doi: 10.1016/j.clinre.2025.102543. Epub 2025 Jan 29.

  PMID: 39884573 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Fatty Liver

Interventions

dapagliflozin; Pioglitazone

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Nirmeen A. Sabry

  Clinical Pharmacy Department - Faculty of Pharmacy - Cairo university

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Dr.

Study Record Dates

• First Submitted: December 1, 2021
• First Posted: February 24, 2022
• Study Start: August 1, 2022
• Primary Completion: January 23, 2024
• Study Completion: July 23, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)