Clinical trial NCT04976283: Effect of Oral Anti-diabetic Medication on Liver Fat in Subjects With Type II Diabetes and Non-alcoholic Fatty Liver
Official title: Which Oral Combination of Anti-diabetes Medication May Work Better in Subjects With Type 2 Diabetes and Nonalcoholic Fatty Liver Disease: a Randomized Control Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
NASH - Nonalcoholic Steatohepatitis
NAFLD
Lead sponsor: Getz Pharma
Sponsor class: INDUSTRY
First posted: 2021-07-26
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in radiologic liver parameters
timeFrame: 12 months
Secondary outcomes:
measure: Change in liver enzymes
timeFrame: 12 months
measure: Change in Fibrosis-4 (FIB-4) Score and NAFLD Fibrosis Score
timeFrame: 12 months
measure: Change in body weight
timeFrame: 12 months
measure: Change in waist circumference (WC)
timeFrame: 12 months
measure: Change in liver fat mass with total body fat (TBF)
timeFrame: 12 months
measure: Change in HbA1C levels (< 7.0%)
timeFrame: 12 months
measure: Change in Fasting Blood Sugar (FBS)
timeFrame: 12 months
measure: Change in Lipid profile
timeFrame: 12 months
Other outcomes:
measure: Change in Urine Albumin to Creatinine Ratio (UACR)
timeFrame: 12 months
measure: Change in Systolic and Diastolic blood pressure
timeFrame: 12 months
Locations:
city: Karachi
country: Pakistan
facility: Aga Khan University Hospital
state: Sindh
Study officials:
References: