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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how adding two medications, dapagliflozin (an SGLT2 inhibitor) and pioglitazone, to insulin can help manage blood sugar levels in people with type 1 diabetes (T1DM). It aims to determine if this combination can lower blood sugar effectively without causing serious issues like ketoacidosis, a dangerous buildup of acids in the blood. The study compares the effects of pioglitazone to a placebo (a harmless pill that resembles the real treatment) to assess the drug's true impact. People with T1DM who struggle to control their blood sugar with insulin might be suitable candidates, especially if they use multiple insulin injections or an insulin pump daily. As a Phase 4 trial, this research helps to understand how the already FDA-approved treatment benefits more patients.

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.

What is the safety track record for dapagliflozin and pioglitazone?

Research has shown that both dapagliflozin and pioglitazone have been used to treat diabetes, providing information about their safety. Dapagliflozin is approved for type 2 diabetes and has been studied for its ability to control blood sugar without causing major side effects, though it may increase the risk of urinary and genital infections.

Pioglitazone, another medication approved by the FDA for type 2 diabetes, can effectively manage blood sugar levels, according to studies. Some individuals might experience weight gain or swelling. Concerns exist about a higher risk of heart failure and bone fractures with pioglitazone, but for many, the benefits can outweigh these risks.

Both medications are generally well-tolerated, but individual reactions vary. Discussing potential risks and benefits with a healthcare provider is important before joining a trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the combination of dapagliflozin and pioglitazone for Type 1 Diabetes because it offers a new approach to managing this condition. Unlike standard treatments that primarily focus on insulin regulation, dapagliflozin works by helping the kidneys remove excess glucose from the bloodstream, which is a unique mechanism for Type 1 Diabetes. Meanwhile, pioglitazone enhances the body's sensitivity to insulin, potentially reducing the amount of insulin needed. This dual-action strategy could lead to better blood sugar control and fewer complications for patients.

What evidence suggests that this trial's treatments could be effective for type 1 diabetes?

Research has shown that dapagliflozin, a type of medication, helps control blood sugar in people with diabetes. Studies have found that it lowers HbA1c levels, a measure of average blood sugar over several months, and can also aid in weight loss—both crucial for managing diabetes. Pioglitazone increases the body's sensitivity to insulin, enhancing its effectiveness. It has improved blood sugar control and lowered the risk of developing type 2 diabetes. In this trial, some participants will receive pioglitazone treatment, while others will receive a placebo. The combination of dapagliflozin and pioglitazone might improve blood sugar control for people with type 1 diabetes without increasing the risk of dangerous acid build-up (ketoacidosis) or low blood sugar (hypoglycemia). This combination therapy aims to provide a more comprehensive approach to managing diabetes by addressing different aspects of the condition. ^{3 5 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3920795/

Do We Still Need Pioglitazone for the Treatment of Type 2 ... Remarkably, pioglitazone was associated with a significant 31–39% reduced risk of all-cause mortality (P = 0.02 to P < 0.001) compared with metformin, whereas ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1010949

Pioglitazone for Diabetes Prevention in Impaired Glucose ... Pioglitazone reduced the risk of conversion of impaired glucose tolerance to type 2 diabetes mellitus by 72% but was associated with significant weight gain ...

3. nature.com nature.com/articles/s41598-019-41854-2

Efficacy and Safety of Pioglitazone Monotherapy in Type 2 ... In primary outcome analysis of 16 studies, pioglitazone monotherapy reduced HbA1c by 0.05% with no significant difference (95% CI: −0.21 to 0.11 ...

4. diabetesjournals.org diabetesjournals.org/care/article/25/3/517/21927/Dose-Response-Effect-of-Pioglitazone-on-Insulin

Dose-Response Effect of Pioglitazone on Insulin Sensitivity ... Pioglitazone improves glycemic control through the dose-dependent enhancement of β-cell function and improved whole-body and hepatic insulin sensitivity.

5. academic.oup.com academic.oup.com/jcem/article/101/5/2056/2804780

Diabetes Incidence and Glucose Tolerance after Termination ... After 2.4 years of PIO treatment, both MI (4.11 ± 0.2 to 8.20 ± 0.4; P < .005) and insulin secretion/insulin resistance (IS/IR) index (3.30 ± 0.15 to 5.88 ± 0.4 ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK544287/

Pioglitazone - StatPearls - NCBI Bookshelf - NIH Pioglitazone is an oral antidiabetic from the thiazolidinedione drug class, FDA approved for treating type 2 diabetes mellitus in adults, as an adjunct to diet ...

7. diabetesjournals.org diabetesjournals.org/care/article/36/Supplement_2/S155/30193/Do-We-Still-Need-Pioglitazone-for-the-Treatment-of

Do We Still Need Pioglitazone for the Treatment of Type 2 ... Remarkably, pioglitazone was associated with a significant 31–39% reduced risk of all-cause mortality (P = 0.02 to P < 0.001) compared with ...

8. nature.com nature.com/articles/s41598-020-72967-8

a meta-analysis of its risks and benefits from prospective ... Pio has salutary effects on MACE. The positive effects are completely offset by the harm they seem to cause by way of heart failure, fractures, and anaemia.