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

Getz Pharma

Status and phase: Unknown; Phase 4

Conditions: NAFLD; Diabetes Mellitus, Type 2; NASH - Nonalcoholic Steatohepatitis

Treatments: Drug: Pioglitazone + Empagliflozin; Drug: Pioglitazone; Drug: Empagliflozin

Study type: Interventional

Funder types: Industry

Identifiers

NCT04976283

AKUH-GTZ-DM-005-21

Details and patient eligibility

About

This randomized clinical trial aims to compare the effect of the pioglitazone and SGLT2 inhibitor combination on liver fat mass, as compared to either drug used alone, with or without background medical therapy of metformin and/or DDP4 inhibitors.

Full description

To compare the effect of pioglitazone with or without Metformin and/or DPP4 inhibitor (no SGLT2 inhibitor) on improvement of NAFLD parameters, versus

The effect of SGLT inhibitor with or without metformin and/or DPP4 inhibitor (no pioglitazone) on NAFLD parameters and versus

Pioglitazone with or without metformin and/or DPP4 inhibitor, plus empagliflozin on improvement of NAFLD parameters.

Enrollment: 123 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

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 use of 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 heavier individuals)
• 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 enrollment or weight loss procedure(bariatric surgery) within same duration
• History of use of SGLT 2 inhibitors, glitazones, Glucagon-like peptide (GLP) 1 agonists 3 months prior to study enrollment as they influence liver fat
• History of use of insulin/sulphonylurea 3 months prior to study enrollment owing to weight 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 substances like heroin, cocaine, amphetamines) based on history and/or laboratory tests
• Drugs known to be associated with hepatic steatosis like steroids, traditional homeopathic medication (likely to contain steroids), methotrexate, valproate, tamoxifen, amiodarone.
• Alcohol use (History of alcoholism or a greater than recommended alcohol intake (> 21 standard drinks on average per week in men and > 14 standard drinks on average per week in women)
• Severe hepatic impairment (ALT levels > 3 times upper limit normal)
• Hepatitis B/C hepatitis (based on positive Hepatitis B surface antigen, Anti Hepatitis C 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 liver functions
• 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 (as estimated by the MDRD equation)
• Chronic heart failure, history of acute coronary artery disease or cerebrovascular accident within 3 months of consent for study enrollment, based on history and/or cardiac imaging
• History of recurrent Urinary Tract Infections (UTI's) or mycotic infections
• Presence of ketones on Urine Analysis

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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123 participants in 3 patient groups

Pioglitazone

Active Comparator group

Description:

The starting dose would be 15mg/day for pioglitazone and 500 to 1500mg per day for metformin (depending on blood glucose levels). Starting dose for DPP4 inhibitors would be 50 to 100mg daily.

Treatment:

Drug: Pioglitazone

Empagliflozin

Active Comparator group

Description:

The starting dose would be 500-1500mg/day of metformin, plus 5/10/12.5mg empagliflozin (depending on blood glucose levels). Starting dose for DPP4 inhibitors would be 50 to 100mg daily.

Treatment:

Drug: Empagliflozin

Pioglitazone + Empagliflozin

Active Comparator group

Description:

The starting dose would be 15mg/day for pioglitazone and 500 to1500mg per day for metformin and 5/10/12.5mg/25mg/day empagliflozin and 50 to 100mg daily for DPP4 inhibitors depending on blood sugar levels.

Treatment:

Drug: Pioglitazone + Empagliflozin