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

Study Overview
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Brief Summary
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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

Detailed Description
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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 labelled study 150 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

Official Title
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Effect of Sodium Glucose Cotransporter Inhibitors on Non Diabetic Fatty Liver Disease Patients

Conditions
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Fatty Liver Disease

Intervention / Treatment
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* Drug: Empagliflozin 10 MG


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Single center clinical randomized trial open labelled study 150 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: life style modification and diet control<br>40 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<br>40 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<br>* non fatty liver non alcoholic patients Will receive empaglifizon sodium glucose cotransporter in minimum dose 10 mg<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fatty Liver Nonalcoholic nondiabetic