Effect of Sodium Glucose Cotransporter Inhibitors on Non Diabetic Fatty Liver Disease Patients (Fatty liver)

Non-alcoholic fatty liver disease (NAFLD) has become a major health problem worldwide with an increasing prevalence ranging from 13% in Africa to 42% in South-East Asia. The term NAFLD includes a variety of diseases, ranging from liver fat deposition in more than 5% of hepatocytes (steatosis-non-alcoholic fatty liver (NAFL)) to necroinflammation and fibrosis (non-alcoholic steatohepatitis (NASH)), which can progress into NASH-cirrhosis, and eventually to hepatocellular carcinoma 1 Lifestyle modifications remain the cornerstone of NAFLD treatment, even though various pharmaceutical interventions are currently under clinical trial. Among them, sodium-glucose co-transporter type-2 inhibitors (SGLT-2i) are emerging as promising agents. Processes regulated by SGLT-2i, such as endoplasmic reticulum (ER) and oxidative stress, low-grade inflammation, autophagy and apoptosis are all implicated in NAFLD pathogenesis 2

In non-DM patients, only a small single center study exists which studied 12 patients under dapagliflozin and 10 patients under teneligliptin, a DPP4 inhibitor, for a total of 12 weeks, showing that after this intervention period, serum transaminases were decreased in both groups, while in the dapagliflozin group, total body water and body fat decreased, leading to decreased total body weight.3

Study Overview

• Status: Completed
• Conditions: Fatty Liver Disease
• Intervention / Treatment: Drug: Empagliflozin 10 MG

Detailed Description

Introduction :

Non-alcoholic fatty liver disease (NAFLD) has become a major health problem worldwide with an increasing prevalence ranging from 13% in Africa to 42% in South-East Asia. The term NAFLD includes a variety of diseases, ranging from liver fat deposition in more than 5% of hepatocytes (steatosis-non-alcoholic fatty liver (NAFLD)) to necroinflammation and fibrosis (non-alcoholic steatohepatitis (NASH)), which can progress into NASH-cirrhosis, and eventually to hepatocellular carcinoma 1 Lifestyle modifications remain the cornerstone of NAFLD treatment, even though various pharmaceutical interventions are currently under clinical trial. Among them, sodium-glucose co-transporter type-2 inhibitors (SGLT-2i) are emerging as promising agents. Processes regulated by SGLT-2i, such as endoplasmic reticulum (ER) and oxidative stress, low-grade inflammation, autophagy and apoptosis are all implicated in NAFLD pathogenesis 2

In non-DM patients, only a small single center study exists which studied 12 patients under dapagliflozin and 10 patients under teneligliptin, a DPP4 inhibitor, for a total of 12 weeks, showing that after this intervention period, serum transaminases were decreased in both groups, while in the dapagliflozin group, total body water and body fat decreased, leading to decreased total body weight.3

Aim of the study :

To evaluate efficacy of sodium glucose cotransporter inhibitors to improve outecomes among non diabetic non alcoholic fatty liver patients

Designs Single center clinical randomized trial open labelle patients of non diabetic non alcoholic fatty liver from outpatient clinic at assiut university will be randomized and recruited into arms Group A Will receive empaglifizon sodium glucose cotransporter in minimum dose 10 mg Group B Will be Instructed for diet control

All patients will be initially evaluated Full history medical history include Age .Sex Family history of DM ,HX OF HTN DRUG INTAKE history of ALCOHOL intake ..smoking Hx of fatigue Examination weight ,BMI ,waist circumference ,skin manifestation of insulin resistance

Investigation :

Liver enzymes (AlT …AST) Serology HCV Ab,HBsAg Fasting blood glucose ,2 hour blood glucoe HBA1C Lipid profile ,urine analysis TSH HOMA R ABDOMINAL US WILL BE DONE FOR ALL PATINTS Assesment of liver steatosis and fibrosis Fibroscan will be done initially for all cases

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Assiut, Egypt, 71515
    • Faculty of Medicine
  • Assiut, Egypt
    • Bahaa Osman

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• non alcoholic fatty liver patients diagnosed at outpatient clinic of Assiut university

Exclusion Criteria:

- DM Patient Patient with viral hepatitis C,B Patient with hypothyroidism Patient with hepatotoxic drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: life style modification and diet control; 33 patient of non alcoholic fatty liver patients and non diabetic only receive life style modification and diet control
Experimental: empaglifizon 10 mg plus life style and diet control; 22 patient of non alcoholic fatty liver patients and non diabetic Will receive empaglifizon in minimum dose 10 mg in addition to life style modification and diet control	Drug: Empagliflozin 10 MG; non fatty liver non alcoholic patients Will receive empaglifizon sodium glucose cotransporter in minimum dose 10 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate efficacy of sodium glucose cotransporter inhibitors to reduce hepatic steatosis and fibrosis among non diabetic non alcoholic fatty liver patients	assessment of fibrosis and steatosis by fiboscan as A CAP score that falls anywhere between 238 to 260 dB/m represents 11-33% fatty change in the liver. A CAP score that falls anywhere between 260 to 290 dB/m represents 34-66% fatty change in the liver. A CAP score that is 290 dB/m or higher represents over 67% fatty change in the liver	3 MONTHS

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Principal Investigator: bahaa osman taha, Assiut University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2023
• Primary Completion (Actual): February 1, 2024
• Study Completion (Actual): April 1, 2024

Study Registration Dates

• First Submitted: January 9, 2023
• First Submitted That Met QC Criteria: January 19, 2023
• First Posted (Actual): January 23, 2023

Study Record Updates

• Last Update Posted (Estimated): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 28, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Fatty Liver Nonalcoholic nondiabetic
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin
• Other Study ID Numbers: Assiut 1989

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