Diabetes Mellitus, Type 2Phase 4NCT04976283
Effect of Oral Anti-diabetic Medication on Liver Fat in Subjects With Type II Diabetes and Non-alcoholic Fatty Liver
A Phase 4 study testing Pioglitazone, Empagliflozin and Pioglitazone + Empagliflozin in people with Diabetes Mellitus, Type 2 and NASH - Nonalcoholic Steatohepatitis, run by Getz Pharma at 1 site in Pakistan.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Type 2, NASH - Nonalcoholic Steatohepatitis, NAFLD
- What is being tested?
- Pioglitazone, Empagliflozin and Pioglitazone + Empagliflozin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 123 participants
- Where
- 1 sitePakistan
- Study dates
- 15 Sep 2021to 15 Nov 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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 locations and contacts
1 site in 1 country.
Pakistan1 site, 1 recruiting
- Recruiting
Aga Khan University Hospital
Karachi, Sindh, 74800
About this study
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
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.
Read the 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.
- Being tested
- Pioglitazone, Empagliflozin, Pioglitazone + Empagliflozin
- Medical subject headings
- Diabetes Mellitus, Type 2, Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PioglitazoneDrug
Also called Zolid
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.
EmpagliflozinDrug
Also called Diampa
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 + EmpagliflozinDrug
Also called Zolid + Diampa
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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Pioglitazone + Empagliflozin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in radiologic liver parameters
Number of participants reported change in liver fat content from baseline, as quantified by fibroscan
Measured: 12 months
Secondary outcomes (8)
Change in liver enzymes
Number of participants reported change in liver enzymes levels including ALT, AST and GGT
Measured: 12 months
Change in Fibrosis-4 (FIB-4) Score and NAFLD Fibrosis Score
Number of participants reported change in FIB-4 Score and NAFLD Fibrosis Score. Fibrosis-4 scores range from 0 to 4, where <1.45 indicates absence of cirrhosis; score between 1.45 - 3.25 are deemed inconclusive and score >3.25 indicates cirrhosis.
Measured: 12 months
Change in body weight
Number of participants reported change in body weight from baseline (treat to target response of at least 5% of baseline at 6 months, 10% baseline over 12 months).
Measured: 12 months
Change in waist circumference (WC)
Number of participants reported change in waist circumference (WC)
Measured: 12 months
Change in liver fat mass with total body fat (TBF)
Comparison of baseline and end of treatment liver fat mass with total body fat (TBF) using a Body Composition Monitor
Measured: 12 months
Change in HbA1C levels (< 7.0%)
Number of participants reported change in HbA1C levels from baseline to end of treatment
Measured: 12 months
Change in Fasting Blood Sugar (FBS)
Number of participants reported change in Fasting Blood Sugar (FBS) from baseline to end of treatment
Measured: 12 months
Change in Lipid profile
Number of participants reported change in Fasting triglycerides (TG), Low-Density Lipoprotein (LDL), High-Density Lipoprotein (HDL) from baseline to end of treatment
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2021
- Study start15 Sep 2021
- Primary completion15 May 2023 (estimated)
- Study completion15 Nov 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 123 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Getz Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Principal investigator, Dr. Najmul Islam, Aga Khan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04976283
- Sponsor's protocol ID
- AKUH-GTZ-DM-005-21
- Status last verified
- Mar 2022
- First submitted
- 19 Jul 2021
- Last updated
- 18 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04976283
- Acronym / sponsor ID
- AKUH-GTZ-DM-005-21
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 123 participants (estimated)
- Lead sponsor
- Getz PharmaIndustry (pharma, biotech, devices)
- Study start
- 15 Sep 2021 (actual)
- Primary completion
- 15 May 2023 (estimated)
- Study completion
- 15 Nov 2023 (estimated)
- First posted
- 26 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Pioglitazone | Active comparator | Drug: PioglitazoneThe 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. |
| Empagliflozin | Active comparator | Drug: EmpagliflozinThe 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. |
| Pioglitazone + Empagliflozin | Active comparator | Drug: Pioglitazone + EmpagliflozinThe 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PioglitazoneAlso: ZolidPioglitazone 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. | Drug | Pioglitazone |
| EmpagliflozinAlso: DiampaEmpagliflozin 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. | Drug | Empagliflozin |
| Pioglitazone + EmpagliflozinAlso: Zolid + DiampaPioglitazone 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). | Drug | Pioglitazone + Empagliflozin |
Primary outcome
Change in radiologic liver parameters
Time frame: 12 months
Number of participants reported change in liver fat content from baseline, as quantified by fibroscan
8 secondary outcomes
Change in liver enzymes
Time frame: 12 months
Change in Fibrosis-4 (FIB-4) Score and NAFLD Fibrosis Score
Time frame: 12 months
Change in body weight
Time frame: 12 months
Change in waist circumference (WC)
Time frame: 12 months
Change in liver fat mass with total body fat (TBF)
Time frame: 12 months
Change in HbA1C levels (< 7.0%)
Time frame: 12 months
Change in Fasting Blood Sugar (FBS)
Time frame: 12 months
Change in Lipid profile
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pioglitazone, Empagliflozin and Pioglitazone + Empagliflozin in people with Diabetes Mellitus, Type 2 and NASH - Nonalcoholic Steatohepatitis, run by Getz Pharma at 1 site in Pakistan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Azra Rizwan, FCPS (+923212655271, azra.rizwan@aku.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in radiologic liver parameters (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2022.