Efficacy and Safety of Dapagliflozin in Patients With Non-alcoholic Steatohepatitis
Status:
Not yet recruiting
Trial end date:
2025-08-01
Target enrollment:
Participant gender:
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).