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| ID | Type | Description | Link |
|---|---|---|---|
| R01DK097554 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
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The primary purpose of this study is to evaluate the efficacy, durability, and mechanism of HbA1c reduction produced by the combination of pioglitazone plus tirzepatide compared to metformin plus sitagliptin in patients with recently diagnosed type 2 diabetes mellitus.
This is a randomized open label controlled 2 arm study (with one of the arms containing 3 sub-groups) which aims to examine the effectiveness and long term effects on HbA1c reduction produced by the combination of pioglitazone plus tirzepatide versus metformin plus sitagliptin in recently diagnosed type 2 diabetes mellitus (T2DM) patients.
A subgroup of patients from group 1 will be invited to participate in a sub-study which lasts for 6 months and aims at exploring the metabolic/molecular mechanisms responsible for the study results. The selection of subjects to each subgroup will be done randomly and the end of sub-study, subjects will continue therapy and follow-up from month 6 on in the main study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group IC | Experimental | Tirzepatide starting at 2.5mg weekly titrated to 15mg weekly (2.5 month 1, 5mg month 2, 10mg month 3 and 15mg at month 4) with Pioglitazone beginning at 15mg daily and ending at 45mg daily (15mg month 1, 30mg month 2 and 45mg at month 3 onwards). |
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| Group II | Active Comparator | Metformin starting at 1000mg XR daily and Sitagliptin 100mg daily at week 4, Metformin will be increased to 200mg. |
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| Group IA | Active Comparator | Tirzepatide will be started at 2.5mg and increased to 15mg by month 4. At month 6, Pioglitazone will be added to the Tirzepatide, 15 mg daily. |
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| Group 1B | Active Comparator | Pioglitazone will be started at 15mg and increased to 45 mg by month 3. At month 6, tirzepatide 2.5mg will be started and increased weekly as tolerated. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tirzepatide | Drug | Tirzepatide:Participants will be initiated on 2.5mg weekly and increase their dose to 5mg at week 4, 10mg at week 8 and 15mg at week 12 as tolerated. |
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| Measure | Description | Time Frame |
|---|---|---|
| number of subjects achieving HbA1c <6.5% at 6 months (Efficacy) | Therapy failure will be determined as HbA1c >6.5% in two consecutive HbA1c measurements 3 months apart. Time to cumulative incidence of therapy failure curves will be created in subjects receiving pioglitazone/tirzepatide versus subjects receiving metformin/sitagliptin | 6 months |
| Number of subjects failing to achieving HbA1c <6.5% Long-term | The failure to achieving HbA1c <6.5% (Durability) at the end of study in subjects receiving pioglitazone/tirzepatide (Group I) versus metformin/sitagliptin (Group II) in two consecutive HbA1c measurements 3 months apart. | month 60 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in insulin sensitivity | Matsuda Index of insulin sensitivity or total glucose disposal measured with the clamp.These are the gold standard methods for quantification insulin sensitivity with the OGTT or a euglycemic clamp | from baseline to end of study (60 months) |
| Change in Beta Cell Function |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Muhammad Abdul-Ghani, MD | Contact | 210-567-6691 | abdulghani@uthscsa.edu | |
| Gozde Baskoy, PhD | Contact | 210-358-7200 | baskoy@uthscsa.edu |
| Name | Affiliation | Role |
|---|---|---|
| Muhammad Abdul-Ghani, MD | The University of Texas Health Science Center at San Antonio | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Health System Texas Diabetic Institute | Recruiting | San Antonio | Texas | 78207 | United States |
De-identified data will be shared with other researchers at study completion when all data are analyzed and as summary results in ClinicalTrials.gov.
At study completion at the time of publication.
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Randomized open label study. There are 2 groups, with 2 sub groups, 1A, 1B and 1C included within Group 1.
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| Pioglitazone | Drug | Pioglitazone: Participants will begin therapy at 15mg daily for the first 4 weeks then increase dose to 30mg at week 4 and to 45 mg at week 8, as tolerated. |
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| Sitagliptin | Drug | Sitagliptin: will be administered as a 100mg dose once daily. |
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| Metformin HCI XR | Drug | Metformin will be administered at a dose of 1000mg for the first 4 weeks and then the dose increased to 2000mg. |
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A calculated value using plasma glucose, insulin and C-peptide concentrations during the Oral Glucose Tolerance Test (OGTT) test. |
| Baseline to end of study (60 months) |
| Change in body weight | Change from study beginning to end, measured in kilograms (kg) | Baseline to end of study (60 months) |
| UT Health Science Center | Recruiting | San Antonio | Texas | 78229 | United States |
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D000098860 | Tirzepatide |
| D000077205 | Pioglitazone |
| D000068900 | Sitagliptin Phosphate |
| ID | Term |
|---|---|
| D000067757 | Glucagon-Like Peptide-1 Receptor |
| D000067756 | Glucagon-Like Peptide Receptors |
| D043562 | Receptors, G-Protein-Coupled |
| D011956 | Receptors, Cell Surface |
| D008565 | Membrane Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011964 | Receptors, Gastrointestinal Hormone |
| D018000 | Receptors, Peptide |
| D045162 | Thiazolidinediones |
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D014230 | Triazoles |
| D011719 | Pyrazines |
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