Dapagliflozin Plus Pioglitazone in T1DM

Can Addition of Pioglitazone to SGLT2 Inhibitor in Type 1 Diabetic Patients Amplify the Decrease in HbA1c and Prevent the Increase in Plasma Ketone Concentration?

Dapagliflozin Plus Pioglitazone in T1DM (NCT03878459) is a Phase 4 interventional studying Type 1 Diabetes Mellitus, sponsored by The University of Texas Health Science Center at San Antonio. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

Purpose: To examine the effect of addition of combination therapy with dapagliflozin plus pioglitazone to insulin on glucose control and plasma ketone concentration in patients with type 1 diabetes (T1DM) Research Design: 120 patients with type 1 diabetes who otherwise are healthy constitute the study population. After screening, eligible subjects will start 4 week run in. At week 4, subjects will receive dapagliflozin for 12 weeks. At week 16, subjects will be randomized to receive in a double blind fashion pioglitazone or placebo for 16 weeks. Methods: the following techniques will be employed in the present study: (1) mixed meal tolerance test; (2) indirect calorimetry; (3) continuous glucose monitoring. Clinical Relevance: the results of the present study will demonstrate that the addition of pioglitazone to SGLT2 inhibitor in T1DM patients produces greater reduction in the HbA1c without increasing risk of ketoacidosis and hypoglycemia.

What Stage of Research Is This?

Phase 4 studies happen after a treatment has been approved by the FDA. They monitor long-term safety, real-world effectiveness, and any rare side effects that only emerge in larger populations over longer periods. Phase 4 results sometimes lead to label changes, additional warnings, or — rarely — withdrawal of approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 120 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Type 1 Diabetes Mellitus subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: - Age \>18 years - T1DM - Good general health - Fasting C-peptide concentration \<0.7 ng/ml - Poor glycemic control (HbA1c=7.0-11.0%) - Treatment with multiple daily insulin injections or insulin pump - Total daily insulin dose ≥0.6 U/kg per day - Stable insulin dose (±4 units) in the preceding three months. - eGFR≥60 ml/min - Weight stable over the preceding 3 months (± 3 pounds) - Do not participate in an excessively heavy exercise program Who Should NOT Join This Trial: - T2DM - Daily insulin dose \<0.6 U/kg per day - Fasting C-peptide \>0.7 ng/ml - HbA1c \<7.0% or \>11.0% - eGFR\<60 ml/min - Hematuria in urine analysis - Pregnancy, lactating, positive pregnancy test or planning to become pregnant in the following year. - Women of child-bearing potential will be requested to use at least two barrier methods before being enrolled in 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 Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: * Age \>18 years * T1DM * Good general health * Fasting C-peptide concentration \<0.7 ng/ml * Poor glycemic control (HbA1c=7.0-11.0%) * Treatment with multiple daily insulin injections or insulin pump * Total daily insulin dose ≥0.6 U/kg per day * Stable insulin dose (±4 units) in the preceding three months. * eGFR≥60 ml/min * Weight stable over the preceding 3 months (± 3 pounds) * Do not participate in an excessively heavy exercise program Exclusion Criteria: * T2DM * Daily insulin dose \<0.6 U/kg per day * Fasting C-peptide \>0.7 ng/ml * HbA1c \<7.0% or \>11.0% * eGFR\<60 ml/min * Hematuria in urine analysis * Pregnancy, lactating, positive pregnancy test or planning to become pregnant in the following year. * Women of child-bearing potential will be requested to use at least two barrier methods before being enrolled in 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

Treatments Being Tested

DRUG

Pioglitazone 45 mg

patients will be started on 15 mg and the dose escalated to the maximal tolerated dose

DRUG

Placebo

PATIENTS WILL RECEIVE PLACEBO

Locations (3)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

University Health System Texas Diabetic Institute

San Antonio, Texas, United States

Endocrinology and Diabetes Center, Rambam Medical Center

Haifa, Israel

Dasman Diabetes Institute

Kuwait City, Kuwait

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT03878459), the sponsor (The University of Texas Health Science Center at San Antonio), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT03878459 clinical trial studying?

Purpose: To examine the effect of addition of combination therapy with dapagliflozin plus pioglitazone to insulin on glucose control and plasma ketone concentration in patients with type 1 diabetes (T1DM) Research Design: 120 patients with type 1 diabetes who otherwise are healthy constitute the study population. After screening, eligible subjects will start 4 week run in. At week 4, subjects will receive dapagliflozin for 12 weeks. At week 16, subjects will be randomized to receive in a double blind fashion pioglitazone or placebo for 16 weeks. Methods: the following techniques will be emplo… The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT03878459?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT03878459?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT03878459. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT03878459. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.