Effect of Oral Anti-diabetic Medication on Liver Fat in Subjects With Type II Diabetes and Non-alcoholic Fatty Liver

Inclusion Criteria:

• Patient who give informed consent voluntarily
• Type 2 diabetic patient having age from 18 years to 60 years
• HbA1C ≥ 7.0 %
• Diabetes diagnosis of ≤ 5 years (longer duration more likely to be associated with useof multiple drug regimens for glycemic control which may affect liver fat mass)
• Either treatment naïve or on metformin alone or metformin/DPP4i combination
• Absolute weight < 100kg; BMI < 45 (fibro scan machine cannot accommodate heavierindividuals)
• Documented hepatosteatosis (If the fibroscan reveals S1 (mild fatty liver: 11-33%fatty liver) to S3 (severe fatty liver: > 67% fatty liver) liver fat

Exclusion Criteria:

• Hba1c ≥ 9% and/or blood sugar > 250mg/dl
• History of uncontrolled Endocrine disorder (for example uncontrolled hypothyroidism,or that requiring frequent dose adjustment, or Cushings syndrome)
• History of anti-obesity medication use within 3 months of consent for study enrollmentor weight loss procedure(bariatric surgery) within same duration
• History of use of SGLT 2 inhibitors, glitazones, Glucagon-like peptide (GLP) 1agonists 3 months prior to study enrollment as they influence liver fat
• History of use of insulin/sulphonylurea 3 months prior to study enrollment owing toweight gain and potential increase in liver fat conferred by these agents
• History of vitamin E use (400mg twice daily) within 3 months of study enrollment
• Drug induced liver disease or active substance abuse (cannabonnoid-derived substanceslike heroin, cocaine, amphetamines) based on history and/or laboratory tests
• Drugs known to be associated with hepatic steatosis like steroids, traditionalhomeopathic medication (likely to contain steroids), methotrexate, valproate,tamoxifen, amiodarone.
• Alcohol use (History of alcoholism or a greater than recommended alcohol intake (> 21standard drinks on average per week in men and > 14 standard drinks on average perweek in women)
• Severe hepatic impairment (ALT levels > 3 times upper limit normal)
• Hepatitis B/C hepatitis (based on positive Hepatitis B surface antigen, Anti HepatitisC antibodies positive
• Autoimmune hepatitis (in case of females), based on positive Anti-nuclear Antibody (ANA) (homogenous, high titre)
• Positive Human Immunodeficiency Virus ( HIV) test as this could influence liverfunctions
• Pregnant or lactating women/ plans for pregnancy over proceeding 13 months
• Obstructive liver disease on the basis of laboratory and imaging studies
• Chronic renal failure, or Glomerular Filtration Rate (GFR) < 30 mls/minute (asestimated by the MDRD equation)
• Chronic heart failure, history of acute coronary artery disease or cerebrovascularaccident within 3 months of consent for study enrollment, based on history and/orcardiac imaging
• History of recurrent Urinary Tract Infections (UTI's) or mycotic infections
• Presence of ketones on Urine Analysis