Type1diabetesPhase 3NCT07056699
SGLT2i, Pioglitazone, and Ketone Production in T1D
A Phase 3 study testing Dapagliflozin 10mg Tab and Pioglitazone 15 MG and 30mg in people with Type1diabetes, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
Trial summary
Participants are being asked to be in a research study. Scientists do research to answer important questions which might help change or improve treatment of participants disease in the future. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Type1diabetes
- What is being tested?
- Dapagliflozin 10mg Tab and Pioglitazone 15 MG and 30mg
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2026to 30 Jun 2027
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >18 years
- T1D
- Other than diabetes, subjects must be in good general health as determined by the investigator based on physical exam, medical history and screening labs.
- Minor deviations may be permitted if:
- The abnormality is not considered clinically significant.
- The deviation does not pose a safety risk or interfere with study participation.
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- The rationale for inclusion is documented in the source records.
- Fasting C-peptide concentration <0.7 ng/ml
- Poor glycemic control (HbA1c=7.0-11.0%)
- Treatment with multiple daily insulin injections (basal plus prandial) or insulin pump
- Total daily insulin dose ≥0.6 U/kg per day
- Stable insulin dose (±4 units) in the preceding three months
- eGFR ≥ 50 ml/min
- Weight stable over the preceding 3 months (± 4 pounds)
- Positive GAD antibody (Glutamic Acid Decarboxylase antibody). *
- Testing for GAD antibodies will be performed during the screening visit. Participants who test positive for GAD antibodies will be eligible for enrollment in the study. Over time, these antibodies may disappear, reducing the likelihood of a positive result during screening. If participant tests negative for GAD antibodies, their medical history will be reviewed to determine whether testing for GAD antibodies was performed at an earlier stage of Type 1 Diabetes (T1D). If prior positive results are confirmed, the participant may be enrolled. If a participant tests positive for antibodies other than GAD, an exception request will be submitted to the Institutional Review Board (IRB) for approval.
Who cannot join
- Type 2 Diabetes (T2D)
- Daily insulin dose <0.6 U/kg per day
- Fasting C-peptide >0.7 ng/ml
- HbA1c <7.0% or >11.0%
- eGFR < 50 ml/min
- Hematuria in urine analysis
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- Pregnancy, lactating, positive pregnancy test or planning to become pregnant in the following year. Women of child-bearing potential will be required to undergo a pregnancy test prior to enrollment and must agree to use effective contraception (at least two barrier methods) for the duration of the study.
- Major organ system disease which includes: (i) malignancy or history of malignancy including bladder cancer; (ii) Congestive heart failure or history of coronary heart disease or any other cardiac disease; (iii) chronic liver disease or LFT >3 times the upper normal level; (iv) History of alcohol or drug abuse; (v) History of chronic lung disease (e.g., COPD, asthma); (vi) history of rheumatic disease; (vii) History of chronic pancreatitis or pancreatic surgery; (viii) History of CVA or TIA (ix) Planned surgery during the study; (x) history of HIV infection or other immune compromised disease; and history of organ transplantation; (xi) patients who take medications, other than insulin, known to affect glucose metabolism, e.g., prednisone.
- Evidence of proliferative diabetic retinopathy
- Patients enrolled in a heavy exercise program
- Patients on ketogenic diet
- History of hospitalization for DKA, hypoglycemia or uncontrolled hyperglycemia in the preceding 6 month.
- Presence of symptoms of poor glycemic control, e.g. polydipsia or polyurea
- History of hypersensitivity to dapagliflozin or pioglitazone
- Participants with a history of radiation exposure exceeding 5 REM within the previous 12 months will be excluded.
- Prior to the screening period, potential participants will be pre-screened either by phone or in person at the Texas Diabetes Institute. Individuals with prior significant radiation exposure will be excluded.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Texas Diabetes Institute
San Antonio, Texas, 78229-3900
Ralph Defronzo, MD, 210-567-6691, defronzo@uthscsa.edu
Aurora Merovci, MD, MPH, 210 358 7409, merovci@uthscsa.edu
About this study
Official title: Protocol V: San Antonio Site Sub Study: Can Pioglitazone Block SGLT2 Inhibitor-induced Stimulation of Lipolysis, Ketone Production and Liver Glucose Production in Type I Diabetic Patients
Participants are being asked to be in a research study. Scientists do research to answer important questions which might help change or improve treatment of participants disease in the future.
In patients with Type 1 Diabetes (T1D), dapagliflozin a Selective Glucose Transporter 2 Inhibitor (SGLT2i) is known to increase production of glucose in the liver, increase breakdown of fats (lipolysis), and increase production of ketones (ketogenesis). Ketones are chemicals produced by the liver when the body breaks down fat for energy instead of glucose. When the level of ketones in the body becomes too high, a condition called ketoacidosis develops. In this study, the study team will investigate whether adding pioglitazone (a medication commonly used to treat type 2 diabetes), can reduce the dapagliflozin - induced liver glucose production, fat break down (lipolysis) and ketone body production (ketogenesis) in patients with T1D.
Read the detailed description
The purpose of this research study is to investigate the effects of dapagliflozin and pioglitazone in the body - specifically, on liver glucose production, breakdown of fat, and ketone production in T1D patients treated with insulin. Subjects with T1D can't make insulin because their pancreas doesn't work properly. This means they need insulin injections to control their blood sugar. But using insulin can sometimes cause low blood sugar and weight gain, making it harder for insulin to work and requiring higher doses. Finding other medicines that can help lower blood sugar in people with T1D and can be used along with insulin would make it easier to manage their blood sugar.
Dapagliflozin is in a class of drugs known as SGLT2i and has been shown to effectively lower blood sugar concentration in T1D patients. These drugs lower blood glucose levels by preventing or reducing the re-absorption of glucose in the kidneys. This results in the release of glucose into the urine. At the same time, SGLT2i drugs stimulate glucose production by the liver, which helps compensate for the loss of glucose into the urine. Also, the use of dapagliflozin in patients with type 1 diabetes was associated with increased risk of ketoacidosis. Ketoacidosis is a serious condition that occurs when the body produces high levels of ketones, leading to increased acidity in the blood. Pioglitazone is in a class of thiazolidinediones and is commonly used to treat high blood sugar levels caused by type 2 diabetes. The investigators believe that the addition of pioglitazone, to dapagliflozin will prevent the risk of ketoacidosis associated with dapagliflozin, and will cause a large reduction in plasma glucose concentration in T1D patients.
- Conditions
- Type1diabetes
- Being tested
- Dapagliflozin 10mg Tab, Pioglitazone 15 MG and 30mg, Placebo
- Keywords
- Selective Glucose Cotransporter 2 inhibitors (SGLT2i), Dapagliflozin, Pioglitazone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dapagliflozin 10mg TabDrug
Also called Farxiga
Dapagliflozin (10 mg/day)
Pioglitazone 15 MG and 30mgDrug
Also called Actos
Pioglitazone (15 mg/day for 2 weeks, then 30 mg/day for 14 weeks)
PlaceboOther
Also called Inert substance
Inert placebo for Pioglitazone
| Study group | Role | What they receive |
|---|---|---|
| Experimental study drug for T1D | Experimental | Dapagliflozin (10 mg/day) + Pioglitazone (15 mg/day for 2 weeks, then 30 mg/day for 14 weeks) Receives: Drug: Dapagliflozin 10mg Tab; Drug: Pioglitazone 15 MG and 30mg |
| Placebo Group for T1D | Placebo comparator | Dapagliflozin (10 mg/day) + Placebo (for 16 weeks) Receives: Drug: Dapagliflozin 10mg Tab; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in endogenous glucose production (EGP)
Infusions of a tracer, ³H-glucose, will begin and continue until the end of the study.
A single dose of empagliflozin (25 mg) by mouth will be taken at 900am. Blood samples will be collected minutes to assess how your body responds to the infused tracers.
This tracer help to measure the rate of endogenous (liver) glucose production. The difference in levels of EGP will be reported from the beginning of the study to a second level taken 16 weeks later.
Measured: Baseline (Week 0) to Week 16
Change in ketone body production ( ketogenesis)
Infusions of tracers, ³H-glucose and U-2H-glycerol or 14C-Glycerol, will begin and continue until the end of the study.
A single dose of empagliflozin (25 mg) by mouth will be taken at 900am. Blood samples will be collected to assess how your body responds to the infused tracers.
This tracer help to measure the rate of ketone body production (ketogenesis). The difference in levels of ketones will be reported from the beginning of the study to a second level taken 16 weeks later.
Measured: Baseline (Week 0) to Week 16
Change in lipolysis (fat breakdown)
Infusions of tracers, U-H-14C-Glycerol or 2H-Glycerol, will begin and continue until the end of the study.
A single dose of empagliflozin (25 mg) by mouth will be taken at 900am. Blood samples will be collected to assess how your body responds to the infused tracers.
This tracer help to measure the rate of lipolysis (fat breakdown). The difference in levels of lipolysis will be reported from the beginning of the study to a second level taken 16 weeks later.
Measured: Baseline (Week 0) to Week 16
Secondary outcomes (3)
Change in HbA1c from baseline (Week 0) to Week 16
HbA1c and CGM metrics provide clinically relevant data on glycemic control and variability. This endpoint assess the metabolic efficacy of adding pioglitazone to dapagliflozin in T1DM.
Measured: Baseline (Week 0) to Week 16
Change in plasma Free Fatty Acid (FFA) from baseline (Week 0) to Week 16.
Measuring free fatty acids directly tests the hypothesis that pioglitazone reduces the risk of SGLT2 inhibitor-associated diabetic ketoacidosis (DKA) by suppressing FFA release.
Measured: Baseline (Week 0) to Week 16
Change in glycerol from baseline (Week 0) to week 16.
To examine the effects of adding pioglitazone (15/30 mg/day) to dapagliflozin (10 mg/day) compared to dapagliflozin (10mg/day) plus placebo in T1DM patients, focusing on lipolysis changes over a 16-week treatment period.
Measured: Baseline (Week 0) to Week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2025
- Study start1 Jul 2026
- Primary completion1 Jun 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type1diabetesStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center at San AntonioThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A cluster randomized, double-blind, placebo-controlled mechanistic study
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- 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 AntonioRalph DeFronzo, MD, Principal investigator, The University of Texas Health Science Center at San Antonio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07056699
- Sponsor's protocol ID
- STUDY00001633 - 504078
- Other IDs
- R01DK024092
- Status last verified
- Jul 2026
- First submitted
- 26 Jun 2025
- Last updated
- 20 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Study participant research data, which is for purposes of statistical analysis and scientific reporting, will be transmitted to and stored at the Diabetes division at UT Health. This will not include the participant's contact or identifying information. Rather, individual participants and their research data will be identified by a unique study identification number. The study data entry and study management systems used by clinical sites and by Diabetes division at UT Health research staff will be secured, and password protected. At the end of the study, all study databases will be de-identified and archived at the Diabetes division at UT Health.
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Protocol V: San Antonio Site Sub Study: Can Pioglitazone Block SGLT2 Inhibitor-induced Stimulation of Lipolysis, Ketone Production and Liver Glucose Production in Type I Diabetic Patients
- ClinicalTrials.gov ID
- NCT07056699
- Acronym / sponsor ID
- STUDY00001633 - 504078
- Conditions
- Type1diabetes
- Keywords
- Selective Glucose Cotransporter 2 inhibitors (SGLT2i), Dapagliflozin, Pioglitazone
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 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
- 1 Jul 2026 (actual)
- Primary completion
- 1 Jun 2027 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 9 Jul 2025 (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.
Participants are being asked to be in a research study. Scientists do research to answer important questions which might help change or improve treatment of participants disease in the future.
In patients with Type 1 Diabetes (T1D), dapagliflozin a Selective Glucose Transporter 2 Inhibitor (SGLT2i) is known to increase production of glucose in the liver, increase breakdown of fats (lipolysis), and increase production of ketones (ketogenesis). Ketones are chemicals produced by the liver when the body breaks down fat for energy instead of glucose. When the level of ketones in the body becomes too high, a condition called ketoacidosis develops. In this study, the study team will investigate whether adding pioglitazone (a medication commonly used to treat type 2 diabetes), can reduce the dapagliflozin - induced liver glucose production, fat break down (lipolysis) and ketone body production (ketogenesis) in patients with T1D.
Detailed description
The purpose of this research study is to investigate the effects of dapagliflozin and pioglitazone in the body - specifically, on liver glucose production, breakdown of fat, and ketone production in T1D patients treated with insulin. Subjects with T1D can't make insulin because their pancreas doesn't work properly. This means they need insulin injections to control their blood sugar. But using insulin can sometimes cause low blood sugar and weight gain, making it harder for insulin to work and requiring higher doses. Finding other medicines that can help lower blood sugar in people with T1D and can be used along with insulin would make it easier to manage their blood sugar.
Dapagliflozin is in a class of drugs known as SGLT2i and has been shown to effectively lower blood sugar concentration in T1D patients. These drugs lower blood glucose levels by preventing or reducing the re-absorption of glucose in the kidneys. This results in the release of glucose into the urine. At the same time, SGLT2i drugs stimulate glucose production by the liver, which helps compensate for the loss of glucose into the urine. Also, the use of dapagliflozin in patients with type 1 diabetes was associated with increased risk of ketoacidosis. Ketoacidosis is a serious condition that occurs when the body produces high levels of ketones, leading to increased acidity in the blood. Pioglitazone is in a class of thiazolidinediones and is commonly used to treat high blood sugar levels caused by type 2 diabetes. The investigators believe that the addition of pioglitazone, to dapagliflozin will prevent the risk of ketoacidosis associated with dapagliflozin, and will cause a large reduction in plasma glucose concentration in T1D patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- A cluster randomized, double-blind, placebo-controlled mechanistic study
| Arm | Type | Receives |
|---|---|---|
| Experimental study drug for T1D | Experimental | Drug: Dapagliflozin 10mg Tab, Drug: Pioglitazone 15 MG and 30mgDapagliflozin (10 mg/day) + Pioglitazone (15 mg/day for 2 weeks, then 30 mg/day for 14 weeks) |
| Placebo Group for T1D | Placebo comparator | Drug: Dapagliflozin 10mg Tab, Other: PlaceboDapagliflozin (10 mg/day) + Placebo (for 16 weeks) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Age >18 years
- T1D
- Other than diabetes, subjects must be in good general health as determined by the investigator based on physical exam, medical history and screening labs.
- Fasting C-peptide concentration <0.7 ng/ml
- Poor glycemic control (HbA1c=7.0-11.0%)
Key exclusion criteria (16 listed)
- Type 2 Diabetes (T2D)
- Daily insulin dose <0.6 U/kg per day
- Fasting C-peptide >0.7 ng/ml
- HbA1c <7.0% or >11.0%
- eGFR < 50 ml/min
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 |
|---|---|---|
| Dapagliflozin 10mg TabAlso: FarxigaDapagliflozin (10 mg/day) | Drug | Experimental study drug for T1D, Placebo Group for T1D |
| Pioglitazone 15 MG and 30mgAlso: ActosPioglitazone (15 mg/day for 2 weeks, then 30 mg/day for 14 weeks) | Drug | Experimental study drug for T1D |
| PlaceboAlso: Inert substanceInert placebo for Pioglitazone | Other | Placebo Group for T1D |
Primary outcome
Change in endogenous glucose production (EGP)
Time frame: Baseline (Week 0) to Week 16
Infusions of a tracer, ³H-glucose, will begin and continue until the end of the study. A single dose of empagliflozin (25 mg) by mouth will be taken at 900am. Blood samples will be collected minutes to assess how your body responds to the infused tracers. This tracer help to measure the rate of endogenous (liver) glucose production. The difference in levels of EGP will be reported from the beginning of the study to a second level taken 16 weeks later.
Change in ketone body production ( ketogenesis)
Time frame: Baseline (Week 0) to Week 16
Infusions of tracers, ³H-glucose and U-2H-glycerol or 14C-Glycerol, will begin and continue until the end of the study. A single dose of empagliflozin (25 mg) by mouth will be taken at 900am. Blood samples will be collected to assess how your body responds to the infused tracers. This tracer help to measure the rate of ketone body production (ketogenesis). The difference in levels of ketones will be reported from the beginning of the study to a second level taken 16 weeks later.
Change in lipolysis (fat breakdown)
Time frame: Baseline (Week 0) to Week 16
Infusions of tracers, U-H-14C-Glycerol or 2H-Glycerol, will begin and continue until the end of the study. A single dose of empagliflozin (25 mg) by mouth will be taken at 900am. Blood samples will be collected to assess how your body responds to the infused tracers. This tracer help to measure the rate of lipolysis (fat breakdown). The difference in levels of lipolysis will be reported from the beginning of the study to a second level taken 16 weeks later.
3 secondary outcomes
Change in HbA1c from baseline (Week 0) to Week 16
Time frame: Baseline (Week 0) to Week 16
Change in plasma Free Fatty Acid (FFA) from baseline (Week 0) to Week 16.
Time frame: Baseline (Week 0) to Week 16
Change in glycerol from baseline (Week 0) to week 16.
Time frame: Baseline (Week 0) to Week 16
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 20 Jul 2026.
- Individual participant dataSharing planned: Yes. Study participant research data, which is for purposes of statistical analysis and scientific reporting, will be transmitted to and stored at the Diabetes division at UT Health. This will not include the participant's contact or identifying information. Rather, individual participants and their research data will be identified by a unique study identification number. The study data entry and study management systems used by clinical sites and by Diabetes division at UT Health research staff will be secured, and password protected. At the end of the study, all study databases will be de-identified and archived at the Diabetes division at UT Health.
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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
Ralph DeFronzo, MD principal investigator
The University of Texas Health Science Center at San Antonio
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dapagliflozin 10mg Tab and Pioglitazone 15 MG and 30mg in people with Type1diabetes, run by The University of Texas Health Science Center at San Antonio at 1 site 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 16 inclusion and 16 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 20 Jul 2026. 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 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. Some participants in this study may receive a placebo. 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 Ralph DeFronzo, MD (210 567 6691, defronzo@uthscsa.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in endogenous glucose production (EGP) (time frame: Baseline (Week 0) to Week 16). The study lists 3 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 20 Jul 2026.