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

NCT04976283 | Unknown Phase 4 DMC

• 1 other identifier: AKUH-GTZ-DM-005-21
• Study Type: interventional
• Target: 123
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Change in radiologic liver parameters

  Number of participants reported change in liver fat content from baseline, as quantified by fibroscan

  12 months

Secondary Outcomes (8)

• Change in liver enzymes

  12 months

• Change in Fibrosis-4 (FIB-4) Score and NAFLD Fibrosis Score

  12 months

• Change in body weight

  12 months

• Change in waist circumference (WC)

  12 months

• Change in liver fat mass with total body fat (TBF)

  12 months

Other Outcomes (2)

• Change in Urine Albumin to Creatinine Ratio (UACR)

  12 months

• Change in Systolic and Diastolic blood pressure

  12 months

Study Arms (3)

Pioglitazone

ACTIVE COMPARATOR

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.

Drug: Pioglitazone

Empagliflozin

ACTIVE COMPARATOR

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.

Drug: Empagliflozin

Pioglitazone + Empagliflozin

ACTIVE COMPARATOR

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.

Drug: Pioglitazone + Empagliflozin

Interventions

Pioglitazone DRUG

Pioglitazone with (or without) metformin and/or DPP4 inhibitor (no SGLT2 inhibitor). The maximum dose for metformin would be 2.5 g/day, while for pioglitazone would be 45mg/day. The maximum dose for DPP4 inhibitor would be 100mg/day.

Also known as: Zolid

Pioglitazone

Empagliflozin DRUG

Empagliflozin with (or without) metformin and/or DPP4 inhibitor (no pioglitazone). The maximum dose for metformin would be 2.5g/day, while for empagliflozin would be 25mg/day depending on follow up blood sugar levels and tolerability. The maximum dose 100mg daily.

Also known as: Diampa

Empagliflozin

Pioglitazone + Empagliflozin DRUG

Pioglitazone with (or without) metformin and/or DPP4 inhibitor, plus empagliflozin. The maximum dose for metformin would be 2.5g/day; for pioglitazone would be 45mg/day and 25mg/day for empagliflozin, and 100mg daily for DPP4 inhibitors (depending on follow up blood sugar levels and tolerability).

Also known as: Zolid + Diampa

Pioglitazone + Empagliflozin

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Getz Pharma: lead

Study Sites (1)

Aga Khan University Hospital

Karachi, Sindh, 74800, Pakistan

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Non-alcoholic Fatty Liver Disease

Interventions

Pioglitazone; empagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Azra Rizwan, FCPS

CONTACT

+923212655271; azra.rizwan@aku.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Endocrinology, Diabetes

Study Record Dates

• First Submitted: July 19, 2021
• First Posted: July 26, 2021
• Study Start: September 15, 2021
• Primary Completion: May 15, 2023
• Study Completion: November 15, 2023
• Last Updated: March 18, 2022

Record last verified: 2022-03

Locations

PA (1)