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

Overview

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 Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Primary Purpose: Treatment
  • Masking: None (Open Label)
• Study Primary Completion Date: February 1, 2024

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 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

Interventions

• Drug: Empagliflozin 10 MG
  • non fatty liver non alcoholic patients Will receive empaglifizon sodium glucose cotransporter in minimum dose 10 mg

Arms, Groups and Cohorts

• No Intervention: life style modification and diet control
  • 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
  • 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

Clinical Trial Outcome Measures

Primary Measures

• To evaluate efficacy of sodium glucose cotransporter inhibitors to reduce hepatic steatosis and fibrosis among non diabetic non alcoholic fatty liver patients
  • Time Frame: 3 MONTHS
  • 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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 70 Years

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • Assiut University
• Provider of Information About this Clinical Study
  • Principal Investigator: Bahaa osman taha, Lecturer of internal medicine – Assiut University