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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if metformin, a medication commonly used for diabetes, can prevent high blood pressure during pregnancy in women with type 1 diabetes. Pregnant women with type 1 diabetes face a high risk of complications like high blood pressure, which can endanger both mother and baby. The trial will compare the effects of adding metformin to usual care against usual care alone. Eligible participants are women who are 12 to 19 weeks pregnant and have a pre-pregnancy diagnosis of type 1 diabetes. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective metformin can benefit more patients.

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.

What is the safety track record for metformin?

Research has shown that metformin is generally safe during pregnancy. Studies have found it can help reduce weight gain in pregnant women, indicating good tolerance. One study focused on women with diabetes and found that metformin did not increase the risk of high blood pressure during pregnancy.

The FDA has approved metformin for managing type 2 diabetes, confirming its safety for that condition. It has been used in pregnant women with diabetes, and data consistently show it is safe for both mothers and babies.

Overall, metformin appears to be a safe option for pregnant women, including those with type 1 diabetes, though individual experiences may vary. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard care for pre-eclampsia in type 1 diabetes, which often involves medications to manage blood pressure and close monitoring, metformin offers a unique approach. Researchers are excited about metformin because it targets insulin sensitivity, which is a different mechanism compared to traditional treatments. This could potentially address the underlying metabolic issues linked to pre-eclampsia in those with type 1 diabetes, offering a more targeted and proactive solution. Additionally, metformin is well-known and widely used, which might make it a more accessible and safe option for pregnant women.

What evidence suggests that metformin might be an effective treatment for pre-eclampsia prevention in type 1 diabetes?

Research suggests that metformin, which participants in this trial may receive, could help prevent high blood pressure problems during pregnancy, especially for women with diabetes. In women without diabetes, studies have shown that metformin might lower the risk of these pregnancy-related issues. Metformin is considered safe to use during pregnancy and has been well-researched for treating type 1 diabetes outside of pregnancy. It reduces certain proteins linked to high blood pressure during pregnancy. Overall, metformin has proven effective and safe for similar conditions, making it a promising option for preventing pre-eclampsia in pregnant women with type 1 diabetes. ^{1 2 6 7 8}

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11438264/

Metformin use and preeclampsia risk in women with diabetes We investigated whether metformin used during pregnancy was associated with an altered risk of developing a hypertensive disorder of pregnancy.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04855513

Prevention of Pre-eclampsia Using Metformin: a ... This is an open label, randomized control trial (RCT) in which high risk for pre-eclampsia pregnant subjects will be randomly assigned to either an ...

3. withpower.com withpower.com/trial/phase-4-pre-eclampsia-6-2019-abcd1

Metformin for Pre-eclampsia Prevention in Type 1 Diabetes 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 ...

4. scielo.cl scielo.cl/article_plus.php?pid=S0717-75262024000500347&tlng=en&lng=es

Metformin for prevention of pre-eclampsia in pregnant ... Pre-eclampsia complicates 2-4% of pregnancies. Metformin is a promising therapeutic candidate as would reduce the secretion of soluble fms-like tyrosine kinase ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40171857/

A narrative review of metformin in pregnancy One study found that metformin use in women living with Type 2 diabetes might increase the risk of having smaller babies. This was especially ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10850184/

Efficacy and safety of metformin during pregnancy: an update The available data consistently indicate reduced weight gain with metformin use during pregnancy compared to controls. This effect is observed ...

7. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/am-pdf/10.1111/dom.16361

A Narrative Review of Metformin in Pregnancy We also consider the evidence for other emerging indications for metformin in pregnancy, such as the prevention and management of pre-eclampsia.

8. diabetesjournals.org diabetesjournals.org/care/article/43/Supplement_1/S183/30619/14-Management-of-Diabetes-in-Pregnancy-Standards

14. Management of Diabetes in Pregnancy Women with type 1 diabetes should be prescribed ketone strips and receive education on diabetic ketoacidosis prevention and detection. DKA ...