Type 2 Diabetes (Adult Onset)Phase 3NCT06246799
Comparative Effectiveness of Two Initial Combination Therapies in Patients With Recent Onset Diabetes
A Phase 3 study testing Tirzepatide, Pioglitazone and Sitagliptin in people with Type 2 Diabetes (Adult Onset), run by The University of Texas Health Science Center at San Antonio at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Type 2 Diabetes (Adult Onset)
- What is being tested?
- Tirzepatide, Pioglitazone and Sitagliptin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 256 participants
- Where
- 2 sitesUnited States
- Study dates
- 7 Nov 2024to 30 Jun 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability of subject to understand and the willingness to sign a written informed consent document.
- Males and females; Age 18-75 years
- Recently (within 5 years) diagnosed Type 2 Diabetes Mellitus (T2DM) patients
- Drug naïve or receiving metformin monotherapy
- HbA1c >6.5% (no limit on upper HbA1c value);
- Willingness to adhere to the investigational product regimen
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- Good general health
- Stable body weight over the preceding 3 months
- Agreement to adhere to Lifestyle Considerations throughout study duration.
Who cannot join
- positive anti-GAD (antibodies to glutamic acid decarboxylase)
- pregnancy or plan of becoming pregnant
- evidence of proliferative diabetic retinopathy,
- plasma creatinine >1.4 females or >1.5 males;
- presence of congestive heart failure (CHF);
- history of cancer (<5 years);
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- prior history of pancreatitis,
- bladder cancer or family history of thyroid tumors;
- presence of hematuria in the urine analysis.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
University Health System Texas Diabetic Institute
San Antonio, Texas, 78207
Muhammad Abdul-Ghani, MD, 210-567-2391, abdulghani@uthscsa.edu
- Recruiting
UT Health Science Center
San Antonio, Texas, 78229
About this study
Official title: Comparative Effectiveness of Two Initial Combination Therapies in Patients With New Onset Diabetes
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.
Read the detailed description
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.
- Conditions
- Type 2 Diabetes (Adult Onset)
- Being tested
- Tirzepatide, Pioglitazone, Sitagliptin, Metformin HCI XR
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TirzepatideDrug
Also called Mounjaro
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.
PioglitazoneDrug
Also called Actos
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.
SitagliptinDrug
Also called Januvia
Sitagliptin: will be administered as a 100mg dose once daily.
Metformin HCI XRDrug
Also called Extended Release Metformin
Metformin will be administered at a dose of 1000mg for the first 4 weeks and then the dose increased to 2000mg.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Tirzepatide; Drug: Pioglitazone |
| Group II | Active comparator | Metformin starting at 1000mg XR daily and Sitagliptin 100mg daily at week 4, Metformin will be increased to 200mg. Receives: Drug: Sitagliptin; Drug: Metformin HCI XR |
| 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. Receives: Drug: Tirzepatide; Drug: Pioglitazone |
| 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. Receives: Drug: Tirzepatide; Drug: Pioglitazone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: month 60
Secondary outcomes (3)
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
Measured: from baseline to end of study (60 months)
Change in Beta Cell Function
A calculated value using plasma glucose, insulin and C-peptide concentrations during the Oral Glucose Tolerance Test (OGTT) test.
Measured: Baseline to end of study (60 months)
Change in body weight
Change from study beginning to end, measured in kilograms (kg)
Measured: Baseline to end of study (60 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2024
- Study start7 Nov 2024
- Primary completion30 Apr 2029 (estimated)
- Study completion30 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 Diabetes (Adult Onset)Studies 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 3
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized open label study. There are 2 groups, with 2 sub groups, 1A, 1B and 1C included within Group 1.
- Masking
- None (open label)
- Enrolment
- 256 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Texas Health Science Center at San Antonio
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Muhammad Abdul-Ghani, MD, Principal investigator, The University of Texas Health Science Center at San Antonio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06246799
- Sponsor's protocol ID
- STUDY00000139
- Other IDs
- R01DK097554
- Status last verified
- Mar 2026
- First submitted
- 30 Jan 2024
- Last updated
- 10 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified data will be shared with other researchers at study completion when all data are analyzed and as summary results in ClinicalTrials.gov.
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparative Effectiveness of Two Initial Combination Therapies in Patients With New Onset Diabetes
- ClinicalTrials.gov ID
- NCT06246799
- Acronym / sponsor ID
- STUDY00000139
- Conditions
- Type 2 Diabetes (Adult Onset)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 256 participants (estimated)
- Lead sponsor
- The University of Texas Health Science Center at San AntonioUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 7 Nov 2024 (actual)
- Primary completion
- 30 Apr 2029 (estimated)
- Study completion
- 30 Jun 2029 (estimated)
- First posted
- 7 Feb 2024 (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.
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.
Detailed description
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Randomized open label study. There are 2 groups, with 2 sub groups, 1A, 1B and 1C included within Group 1.
| Arm | Type | Receives |
|---|---|---|
| Group IC | Experimental | Drug: Tirzepatide, Drug: PioglitazoneTirzepatide 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). |
| Group II | Active comparator | Drug: Sitagliptin, Drug: Metformin HCI XRMetformin starting at 1000mg XR daily and Sitagliptin 100mg daily at week 4, Metformin will be increased to 200mg. |
| Group IA | Active comparator | Drug: Tirzepatide, Drug: PioglitazoneTirzepatide 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. |
| Group 1B | Active comparator | Drug: Tirzepatide, Drug: PioglitazonePioglitazone 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Ability of subject to understand and the willingness to sign a written informed consent document.
- Males and females; Age 18-75 years
- Recently (within 5 years) diagnosed Type 2 Diabetes Mellitus (T2DM) patients
- Drug naïve or receiving metformin monotherapy
- HbA1c >6.5% (no limit on upper HbA1c value);
Key exclusion criteria (9 listed)
- positive anti-GAD (antibodies to glutamic acid decarboxylase)
- pregnancy or plan of becoming pregnant
- evidence of proliferative diabetic retinopathy,
- plasma creatinine >1.4 females or >1.5 males;
- presence of congestive heart failure (CHF);
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 |
|---|---|---|
| TirzepatideAlso: MounjaroTirzepatide: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. | Drug | Group 1B, Group IA, Group IC |
| PioglitazoneAlso: ActosPioglitazone: 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. | Drug | Group 1B, Group IA, Group IC |
| SitagliptinAlso: JanuviaSitagliptin: will be administered as a 100mg dose once daily. | Drug | Group II |
| Metformin HCI XRAlso: Extended Release MetforminMetformin will be administered at a dose of 1000mg for the first 4 weeks and then the dose increased to 2000mg. | Drug | Group II |
Primary outcome
number of subjects achieving HbA1c <6.5% at 6 months (Efficacy)
Time frame: 6 months
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
Number of subjects failing to achieving HbA1c <6.5% Long-term
Time frame: month 60
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.
3 secondary outcomes
Change in insulin sensitivity
Time frame: from baseline to end of study (60 months)
Change in Beta Cell Function
Time frame: Baseline to end of study (60 months)
Change in body weight
Time frame: Baseline to end of study (60 months)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2026.
- Individual participant dataSharing planned: Yes. De-identified data will be shared with other researchers at study completion when all data are analyzed and as summary results in ClinicalTrials.gov.
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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.
Muhammad Abdul-Ghani, MD principal investigator
The University of Texas Health Science Center at San Antonio
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tirzepatide, Pioglitazone and Sitagliptin in people with Type 2 Diabetes (Adult Onset), run by The University of Texas Health Science Center at San Antonio at 2 sites in United States.
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 9 inclusion and 9 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: looking for participants now, as of the sponsor's last update on 10 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Muhammad Abdul-Ghani, MD (210-567-6691, abdulghani@uthscsa.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
number of subjects achieving HbA1c <6.5% at 6 months (Efficacy) (time frame: 6 months). The study lists 2 primary outcomes in all. 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 10 Mar 2026.