Dapagliflozin + Pioglitazone for Type 1 Diabetes

Recruiting at 2 trial locations

Overseen By Muhammad Abdul-Ghani, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

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

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

120 Participants Needed

Trial Summary

What is the purpose of 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.

Will I have to stop taking my current medications?

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

Is Dapagliflozin safe for humans?

Dapagliflozin has been used safely in humans for type 2 diabetes and chronic kidney disease, but it is no longer authorized for type 1 diabetes. It may cause some side effects like genital infections and mild urinary tract infections, especially in women. ^{1 2 3 4 5}

How does the drug Dapagliflozin + Pioglitazone differ from other treatments for type 1 diabetes?

Dapagliflozin is a drug that works by helping the kidneys remove sugar from the body through urine, and it is typically used for type 2 diabetes. However, it is no longer authorized for type 1 diabetes, making its combination with Pioglitazone unique but not standard for type 1 diabetes treatment. ^{1 2 4 5 6}

Eligibility Criteria

Adults over 18 with Type 1 Diabetes, HbA1c levels between 7.0-11.0%, and on a stable insulin dose can join this trial. They should be in good health, not heavily exercising, or planning pregnancy. Excluded are those sensitive to the drugs tested, with kidney issues (eGFR<60), other major diseases, recent severe diabetes complications, or on glucose-affecting meds besides insulin.

Inclusion Criteria

Do not participate in an excessively heavy exercise program

My insulin dose has been stable for the last 3 months.

I take 0.6 units or more of insulin per kilogram of my body weight daily.

Exclusion Criteria

My kidney function is reduced.

I am allergic to dapagliflozin or pioglitazone.

I do not have major organ diseases, a history of serious illness, or take medication affecting glucose, other than insulin.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in

Eligible subjects start a 4-week run-in period

4 weeks

Treatment Phase 1

Participants receive dapagliflozin for 12 weeks

12 weeks

Treatment Phase 2

Participants are randomized to receive pioglitazone or placebo for 16 weeks

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Dapagliflozin
• Pioglitazone 45 mg

Trial Overview The study tests if adding dapagliflozin and pioglitazone to insulin therapy improves blood sugar control in Type 1 Diabetes without increasing ketoacidosis or hypoglycemia risk. Participants will first take dapagliflozin for 12 weeks then randomly get either pioglitazone or placebo for another 16 weeks.

Participant Groups

Group I: Intervention Experimental Treatment 1 Intervention

pioglitazone treatment

Group II: control Placebo Group 1 Intervention

subjects will receive placebo

Who Is Running the Clinical Trial?

The University of Texas Health Science Center at San Antonio

Lead Sponsor

Trials

486

Recruited

92,500+

Findings from Research

Dapagliflozin is an effective treatment for type 2 diabetes, proven through multiple controlled clinical trials that assess its efficacy, safety, and tolerability.

It is approved by the FDA for use as a standalone therapy or in combination with other glucose-lowering medications, including insulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of Diabetes Mellitus. Davis, PN., Ndefo, UA., Oliver, A.[2021]

Dapagliflozin (Forxiga) is no longer authorized for the treatment of type 1 diabetes mellitus, indicating a significant change in its regulatory status.

This decision reflects safety concerns or efficacy issues that may have arisen from clinical evaluations or post-marketing surveillance, emphasizing the importance of ongoing drug safety assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin no longer licensed for type 1 diabetes. [2022]

Dapagliflozin (Farxiga) is approved for reducing the risk of declining kidney function and kidney failure in adults with chronic kidney disease, regardless of whether they have type 2 diabetes.

It also helps lower the risk of cardiovascular death and hospitalization for heart failure, highlighting its efficacy in managing both kidney and heart health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidiabetic Drug Approved to Reduce Risk of Kidney Disease. Aschenbrenner, DS.[2023]

Dapagliflozin (DAPA) is an effective SGLT2 inhibitor for treating type 2 diabetes, showing favorable pharmacokinetics and pharmacodynamics that help lower blood sugar levels while having beneficial effects on other metabolic risk factors.

While DAPA is generally safe, it carries an increased risk of genital and urinary infections, and concerns about bladder cancer and cardiovascular safety remain, prompting the FDA to seek further data on these issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics and clinical efficacy of dapagliflozin for the treatment of type 2 diabetes. Maranghi, M., Carnovale, A., Durante, C., et al.[2021]

Dapagliflozin effectively lowers blood sugar levels and glycated hemoglobin (HbA1c) in patients with type 2 diabetes, with a low risk of hypoglycemia and additional benefits like weight loss and reduced blood pressure.

While it is generally safe, dapagliflozin can increase the risk of genital infections, particularly in women, and its efficacy may be reduced in patients with kidney issues; ongoing trials are investigating its potential cardiovascular and renal protective effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dapagliflozin (forxiga®) : SGLT 2 cotransporter inhibitor as glucose-lowering agent in type 2 diabetes]. Scheen, AJ.[2021]

The fixed-combination drug product (FCDP) of dapagliflozin and metformin extended release was found to be bioequivalent to the individual tablets, meaning it provides the same effectiveness in managing blood sugar levels for type 2 diabetes patients.

The study, involving 40 healthy participants, showed that both the FCDP and individual tablets were well tolerated with no serious adverse events, indicating a safe alternative for patients looking to reduce their pill burden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence of Dapagliflozin/Metformin Extended-release Fixed-combination Drug Product and Single-component Dapagliflozin and Metformin Extended-release Tablets in Healthy Russian Subjects. Khomitskaya, Y., Tikhonova, N., Gudkov, K., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of Diabetes Mellitus. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Dapagliflozin no longer licensed for type 1 diabetes. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Antidiabetic Drug Approved to Reduce Risk of Kidney Disease. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics and clinical efficacy of dapagliflozin for the treatment of type 2 diabetes. [2021]

5. Belgium pubmed.ncbi.nlm.nih.gov

[Dapagliflozin (forxiga®) : SGLT 2 cotransporter inhibitor as glucose-lowering agent in type 2 diabetes]. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Bioequivalence of Dapagliflozin/Metformin Extended-release Fixed-combination Drug Product and Single-component Dapagliflozin and Metformin Extended-release Tablets in Healthy Russian Subjects. [2021]