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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in radiologic liver parameters | Number of participants reported change in liver fat content from baseline, as quantified by fibroscan | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in liver enzymes | Number of participants reported change in liver enzymes levels including ALT, AST and GGT | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Urine Albumin to Creatinine Ratio (UACR) | Number of participants reported change in Urine Albumin to Creatinine Ratio (UACR) from baseline to end of treatment | 12 months |
| Change in Systolic and Diastolic blood pressure |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Azra Rizwan, FCPS | Contact | +923212655271 | azra.rizwan@aku.edu |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Aga Khan University Hospital | Recruiting | Karachi | Sindh | 74800 | Pakistan |
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| 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. |
|
|
| 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). |
|
|
| 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). | 12 months |
| Change in waist circumference (WC) | Number of participants reported change in waist circumference (WC) | 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 | 12 months |
| Change in HbA1C levels (< 7.0%) | Number of participants reported change in HbA1C levels from baseline to end of treatment | 12 months |
| Change in Fasting Blood Sugar (FBS) | Number of participants reported change in Fasting Blood Sugar (FBS) from baseline to end of treatment | 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 | 12 months |
Number of participants reported change in Systolic and Diastolic blood pressure from baseline to end of treatment
| 12 months |
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D065626 | Non-alcoholic Fatty Liver Disease |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D005234 | Fatty Liver |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D000077205 | Pioglitazone |
| C570240 | empagliflozin |
| ID | Term |
|---|---|
| D045162 | Thiazolidinediones |
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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