Metformin for Pre-eclampsia Prevention in Type 1 Diabetes

Overseen By Maisa N Feghali, MD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Maisa N. Feghali, MD

Disqualifiers: Renal insufficiency, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Until delivery

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Although major advancements have been made in improving glycemic management in type 1 diabetes mellitus (DM), women entering pregnancy with type 1 DM continue to be at dramatically increased risk for adverse maternal and neonatal outcomes, including hypertensive disorders of pregnancy (HDP). At present, there is a lack of effective preventive interventions for HDP, which are associated with significant maternal and neonatal morbidity and mortality. Clinical and in vitro data have shown promise for metformin in prevention of HDP in non-diabetic women. Metformin has a reassuring fetal safety profile and has been well studied in type 1 DM outside of pregnancy. The hypothesis to be tested in this application is that compared to usual care, daily oral metformin therapy initiated prior to 20 weeks' gestation in women with type 1 DM reduces the frequency of HDP.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your healthcare provider.

Is metformin safe for use during pregnancy?

Metformin is generally considered safe during pregnancy and is commonly used to treat gestational diabetes. Studies suggest it may also help reduce the risk of pre-eclampsia, a serious pregnancy complication. ^{1 2 3 4 5}

How does the drug metformin differ from other treatments for preventing pre-eclampsia in type 1 diabetes?

Metformin is unique because it not only helps manage blood sugar levels but also reduces the risk of pre-eclampsia by improving blood vessel function and reducing harmful factors in the blood. Unlike other treatments, it is safe during pregnancy and can cross the placenta, potentially offering protective benefits to both mother and baby. ^{2 3 4 6 7}

What data supports the effectiveness of the drug Metformin for preventing pre-eclampsia in women with type 1 diabetes?

Research suggests that Metformin, a drug commonly used for gestational diabetes, may help reduce the risk of pre-eclampsia (a pregnancy complication characterized by high blood pressure) by promoting healthy blood vessel changes. Studies have shown it can lower the incidence of high blood pressure disorders in pregnancy for those with type 2 and gestational diabetes, indicating potential benefits for type 1 diabetes as well. ^{3 6 7 8 9}

Who Is on the Research Team?

Maisa N Feghali, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for pregnant women aged 18-50 with type 1 diabetes, between 12 and just under 20 weeks of gestation. It's not suitable for those with multiple pregnancies, kidney issues, significant protein in urine, liver disease, inflammatory bowel disease, major blood disorders or known metformin allergies.

Inclusion Criteria

I was diagnosed with type 1 diabetes before becoming pregnant.

I am pregnant, between 18 to 50 years old, and in my second trimester.

Exclusion Criteria

I do not have severe kidney, liver, bowel, or major blood disorders.

You have had a bad reaction to metformin before.

There are signs of a major birth defect or genetic condition in the baby on the ultrasound.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily oral metformin therapy initiated prior to 20 weeks' gestation

Until delivery

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-6 weeks postpartum

What Are the Treatments Tested in This Trial?

Interventions

• Metformin

Trial Overview The study tests if taking metformin before the 20th week of pregnancy can reduce high blood pressure-related complications compared to usual care in women with type 1 diabetes. Metformin is a medication typically used to manage diabetes and has been shown safe outside pregnancy.

How Is the Trial Designed?

Group I: Metformin Experimental Treatment 1 Intervention

Group II: Usual care Active Control 1 Intervention

Metformin is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Glucophage for:

• Type 2 diabetes

Approved in United States as Glucophage for:

• Type 2 diabetes

Approved in Canada as Glucophage for:

• Type 2 diabetes

Approved in Japan as Glucophage for:

• Type 2 diabetes

Approved in China as Glucophage for:

• Type 2 diabetes

Approved in Switzerland as Glucophage for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

Maisa N. Feghali, MD

Lead Sponsor

Trials

3

Recruited

130+

Published Research Related to This Trial

The PI2 Trial is a phase II clinical study involving 150 women with preterm pre-eclampsia, testing the efficacy of extended-release metformin compared to a placebo, with the primary goal of delaying delivery by at least 5 days.

Metformin is already known to be safe during pregnancy and may provide a new therapeutic option to manage preterm pre-eclampsia, potentially improving outcomes for both mothers and their babies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double blind, randomised, placebo-controlled trial to evaluate the efficacy of metformin to treat preterm pre-eclampsia (PI2 Trial): study protocol. Cluver, C., Walker, SP., Mol, BW., et al.[2023]

Citations

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

Optimal glycemic control, pre-eclampsia, and gestational hypertension in women with type 1 diabetes in the diabetes and pre-eclampsia intervention trial. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

What is the role of glycemic control in the development of preeclampsia among women with type 1 diabetes? [2022]

3. England pubmed.ncbi.nlm.nih.gov

A double blind, randomised, placebo-controlled trial to evaluate the efficacy of metformin to treat preterm pre-eclampsia (PI2 Trial): study protocol. [2023]

4. Brazil pubmed.ncbi.nlm.nih.gov

Evaluation of Preeclampsia Results after Use of Metformin in Gestation: Systematic Review and Meta-analysis. [2023]

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

Metformin Exposure and Risk of Hypertensive Disorders of Pregnancy in Patients with Type 2 Diabetes. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Metformin, pre-eclampsia, and pregnancy outcomes in women with polycystic ovary syndrome. [2013]

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

Metformin, the aspirin of the 21st century: its role in gestational diabetes mellitus, prevention of preeclampsia and cancer, and the promotion of longevity. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Metformin for prevention of hypertensive disorders of pregnancy in women with gestational diabetes or obesity: systematic review and meta-analysis of randomized trials. [2019]

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

Preeclampsia and diabetes. [2022]