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

NCT ID: NCT04976283

Last Updated: 2022-03-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

123 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-09-15

Study Completion Date

2023-11-15

Brief Summary

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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

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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.

Conditions

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Diabetes Mellitus, Type 2 NASH - Nonalcoholic Steatohepatitis NAFLD

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Pioglitazone

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.

Group Type ACTIVE_COMPARATOR

Pioglitazone

Intervention Type 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.

Empagliflozin

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.

Group Type ACTIVE_COMPARATOR

Empagliflozin

Intervention Type 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.

Pioglitazone + Empagliflozin

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.

Group Type ACTIVE_COMPARATOR

Pioglitazone + Empagliflozin

Intervention Type 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).

Interventions

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Pioglitazone

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.

Intervention Type DRUG

Empagliflozin

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.

Intervention Type DRUG

Pioglitazone + Empagliflozin

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).

Intervention Type DRUG

Other Intervention Names

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Zolid Diampa Zolid + Diampa

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Getz Pharma

INDUSTRY

Sponsor Role lead

Responsible Party

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Dr. Najmul Islam

Professor Endocrinology, Diabetes

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Aga Khan University Hospital

Karachi, Sindh, Pakistan

Site Status RECRUITING

Countries

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Pakistan

Central Contacts

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Azra Rizwan, FCPS

Role: CONTACT

+923212655271

Other Identifiers

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AKUH-GTZ-DM-005-21

Identifier Type: -

Identifier Source: org_study_id

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