Pioglitazone + Dapagliflozin for Type 1 Diabetes

Overseen By Aurora Merovci, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: The University of Texas Health Science Center at San Antonio

Must be taking: Insulin

Must not be taking: Prednisone

Disqualifiers: T2DM, Pregnancy, Major organ disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding pioglitazone, a thiazolidinedione medication, to dapagliflozin, a blood sugar-lowering medication, can help individuals with Type 1 Diabetes manage their condition more effectively. Dapagliflozin, a current treatment, may cause the liver to produce excess glucose and ketones, leading to issues like ketoacidosis. By including pioglitazone, researchers aim to reduce these side effects. Eligible participants have Type 1 Diabetes with poor blood sugar control and regularly use insulin. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications, but you cannot take medications other than insulin that affect glucose metabolism, like prednisone.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that combining dapagliflozin and pioglitazone effectively lowers blood sugar levels. Dapagliflozin, used for type 1 diabetes, aids in weight loss and reduces insulin needs but may increase the risk of ketoacidosis, a condition where excessive acids accumulate in the body, posing a concern for those with type 1 diabetes.

Adding pioglitazone, a medication for type 2 diabetes, lowers blood sugar levels and carries a lower risk of major heart problems, though it can cause some weight gain. Research suggests that using both medications together may result in less weight gain compared to pioglitazone alone. Overall, these treatments are generally well-tolerated, but awareness of possible side effects like ketoacidosis or weight changes is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard insulin-based therapies for Type 1 Diabetes, this investigational treatment combines dapagliflozin and pioglitazone, offering a novel approach. Dapagliflozin helps the body eliminate excess glucose through urine, while pioglitazone improves the body's response to insulin by targeting insulin resistance, a unique mechanism for Type 1 Diabetes. Researchers are excited because this combination could provide better blood sugar control and potentially reduce the burden of frequent insulin injections.

What evidence suggests that this trial's treatments could be effective for Type 1 Diabetes?

This trial will evaluate the combination of dapagliflozin and pioglitazone for Type 1 Diabetes. Studies have shown that adding dapagliflozin to insulin treatment can improve blood sugar control and aid in weight loss for people with Type 1 Diabetes. Research also indicates that pioglitazone can lower HbA1c levels, a measure of long-term blood sugar control. Scientists are investigating whether using dapagliflozin and pioglitazone together can reduce the liver's production of sugar and ketones. Early results suggest this combination might help manage blood sugar and lower the risk of ketoacidosis, a serious condition caused by high ketone levels. Overall, this combination aims to enhance blood sugar control and diabetes management. Participants in this trial will receive either the combination of dapagliflozin and pioglitazone or dapagliflozin with a placebo. ^{2 3 6 7 8}

Who Is on the Research Team?

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

Are You a Good Fit for This Trial?

This trial is for individuals with Type 1 Diabetes. Participants should be interested in how a combination of medications might affect their body's production of glucose, breakdown of fats, and ketone levels.

Inclusion Criteria

My overall health is good, as confirmed by recent medical tests.

Fasting C-peptide concentration <0.7 ng/ml

HbA1c between 7.0% and 11.0%

Exclusion Criteria

Patients enrolled in a heavy exercise program

Patients on ketogenic diet

I have been diagnosed with type 2 diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Dapagliflozin (10 mg/day) with either Pioglitazone or Placebo for 16 weeks to study effects on liver glucose production, lipolysis, and ketone production

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dapagliflozin
• Pioglitazone

Trial Overview The study tests if adding Pioglitazone to Dapagliflozin (SGLT2i) can reduce the liver's glucose production and fat breakdown, as well as lower ketone body production in Type 1 Diabetes patients.

How Is the Trial Designed?

Group I: Experimental study drug for T1D Experimental Treatment 2 Interventions

Dapagliflozin (10 mg/day) + Pioglitazone (15 mg/day for 2 weeks, then 30 mg/day for 14 weeks)

Group II: Placebo Group for T1D Placebo Group 2 Interventions

Dapagliflozin (10 mg/day) + Placebo (for 16 weeks)

Who Is Running the Clinical Trial?

The University of Texas Health Science Center at San Antonio

Lead Sponsor

Trials

486

Recruited

92,500+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07056699

SGLT2i, Pioglitazone, and Ketone Production in T1D The purpose of this research study is to investigate the effects of Dapagliflozin and Pioglitazone in the body - specifically, on liver glucose production, ...

2. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.15526

A multicentre, double‐blind, placebo‐controlled, randomized ... Pioglitazone administration resulted in a significant reduction in HbA1c levels (from 7.80% ± 0.72% to 7.27% ± 0.82%) compared with placebo ( ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10642354/

SGLT2 Inhibitors in the Management of Type 1 Diabetes ... The results of the DEPICT studies showed that the adjunct of dapagliflozin therapy resulted in improved HbA1c and reduced body weight, without ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT03878459/dapagliflozin-plus-pioglitazone-in-t1dm

Dapagliflozin Plus Pioglitazone in T1DM Purpose: To examine the effect of addition of combination therapy with dapagliflozin plus pioglitazone to insulin on glucose control and plasma ...

5. nature.com nature.com/articles/s41598-024-84487-w

Combination of dapagliflozin and pioglitazone lacks ... Using pioglitazone and dapagliflozin in monotherapy, as well as their combination, the obtained results showed restoration of the kidney ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06922656

Can the Addition of Pioglitazone to SGLT2 Inhibitor in Type ... Previous data from our clinical trial has demonstrated that the combination of dapagliflozin plus pioglitazone cause robust decrease in the plasma glucose ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0168822723004461

Pioglitazone, SGLT2 inhibitors and their combination for ... Pioglitazone was associated with a lower risk of MACE (aHR 0.82, 95 % CI 0.71–0.94) and there was no difference in risk of heart failure compared with the ...

8. diabetesjournals.org diabetesjournals.org/care/article/35/7/1473/30378/Effects-of-Dapagliflozin-an-SGLT2-Inhibitor-on

Effects of Dapagliflozin, an SGLT2 Inhibitor, on HbA 1c , Body ... Patients receiving pioglitazone alone had greater weight gain (3 kg) than those receiving dapagliflozin plus pioglitazone (0.7–1.4 kg) at week 48. Through 48 ...