Metformin for Prediabetes in Pregnancy

Overseen By Heidi Leftwich, DO

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: Gianna Wilkie

Must not be taking: Metformin

Disqualifiers: Diabetes, Liver failure, Renal failure, 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: 2

Duration: From 14 weeks gestation 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 type 2 diabetes, can reduce pregnancy complications in women with prediabetes. Researchers seek to discover if metformin can lower the likelihood of having large babies at birth compared to regular prenatal care. Participants should be pregnant women with prediabetes, as determined by specific blood sugar levels, receiving care at UMass Memorial Medical Center. As a Phase 4 trial, this research explores how this FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are already taking metformin for other reasons, you cannot participate in this study.

What is the safety track record for metformin?

Research has shown that metformin is generally safe during pregnancy and does not increase the risk of major birth defects. However, some studies have reported mixed results regarding its effects on birth outcomes. For example, metformin has been associated with a higher chance of early birth and lower birth weight, but these effects can vary based on its use.

The FDA has already approved metformin to help manage blood sugar levels in people with diabetes, indicating it is well-tolerated by many. The current study is in a later stage, suggesting the treatment has been tested in many people before, with few serious safety concerns. Prospective participants in a clinical trial with metformin may find this information helpful in understanding its safety. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard prenatal care for prediabetes, which typically involves lifestyle changes and monitoring blood sugar levels, Metformin offers a proactive pharmacological approach. Metformin is unique because it not only helps in managing blood sugar levels but also improves insulin sensitivity, which is crucial during pregnancy. Researchers are excited about this treatment because it could potentially reduce the risk of gestational diabetes and related complications, offering a new avenue for managing prediabetes in pregnancy safely and effectively.

What evidence suggests that metformin might be an effective treatment for prediabetes in pregnancy?

Research has shown that using metformin during pregnancy can help mothers gain less weight and lower the risk of some pregnancy complications. In this trial, participants in the metformin arm will take a 500 mg tablet orally twice a day, starting at 14 weeks of pregnancy until delivery. Studies have found that metformin leads to fewer negative pregnancy outcomes compared to starting insulin. It can also reduce the chances of low blood sugar in newborns and lessen the need for newborns to be admitted to intensive care. Metformin is already approved for treating certain types of diabetes and effectively controls blood sugar levels. This evidence suggests that metformin could help manage prediabetes during pregnancy. ^{1 2 5 6 7}

Who Is on the Research Team?

Gianna L Wilkie, MD

Principal Investigator

UMass Memorial Health

Are You a Good Fit for This Trial?

This trial is for pregnant women receiving care at UMass Memorial Medical Center, who have prediabetes indicated by specific blood sugar tests before the 14th week of gestation. They must be able to consent in writing. It's not for those under 18, with pre-existing diabetes, on metformin already, or if they have liver/renal/heart failure, sensitivity to metformin, a multiple pregnancy or noted fetal defects.

Inclusion Criteria

You received pregnancy and delivery care at University of Massachusetts (UMass) Memorial Medical Center.

Patients able to provide written informed consent

Pregnant women with early signs of high blood sugar levels.

Exclusion Criteria

I am under 18 years old.

I am already taking metformin for a health condition.

You have experienced a miscarriage before being selected for the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 14 weeks gestation

1 visit (in-person)

Treatment

Participants are randomized to receive either metformin or standard prenatal care from 14 weeks of pregnancy until delivery

From 14 weeks gestation until delivery

Routine prenatal visits

Follow-up

Participants are monitored for obstetric, maternal, and neonatal outcomes until the 6-week postpartum visit

6 weeks postpartum

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Metformin

Trial Overview The study is testing whether metformin can reduce the risk of having large babies among pregnant women with prediabetes compared to standard treatment without metformin. The goal is to see if this drug can improve outcomes for these pregnancies.

How Is the Trial Designed?

Group I: Metformin Experimental Treatment 1 Intervention

Study subjects will be randomized to the metformin medication arm. They will take a 500 mg tablet orally twice a day starting at 14 weeks of pregnancy until delivery.

Group II: Standard of Care Active Control 1 Intervention

Study subjects will be randomized to standard of care and receive routine prenatal care without further intervention for their prediabetes.

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?

Gianna Wilkie

Lead Sponsor

Trials

2

Recruited

310+

Citations

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

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

2. diabetesjournals.org diabetesjournals.org/care/article/47/9/1688/157019/Perinatal-Outcomes-Associated-With-Metformin-Use

Perinatal Outcomes Associated With Metformin Use During ... Those who received metformin had a reduction in neonatal hypoglycemia and NICU admissions. The risks of other neonatal outcomes were similar ...

3. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2812641

Metformin Plus Insulin for Preexisting Diabetes or ... Using metformin plus insulin to treat preexisting type 2 or gestational diabetes diagnosed early in pregnancy did not reduce a composite neonatal adverse ...

4. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.16115

Metformin and risk of adverse pregnancy outcomes among ... Our study suggests that, compared to initiating insulin, initiating metformin is associated with decreased risks of adverse pregnancy outcomes ...

5. nature.com nature.com/articles/s41598-021-88650-5

Impact of metformin treatment during pregnancy on ... Metformin for any indication during pregnancy is associated with lower GWG and a modest reduced risk of pre-eclampsia, but increased gastrointestinal side- ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04523363

Metformin Versus Standard of Care Treatment in Pregnant ... The purpose of this study is to assess if metformin reduces adverse outcomes associated with prediabetes in pregnancy. Our hypothesis is that pregnant women ...

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

A narrative review of metformin in pregnancy: Navigating ... However, while metformin use has not been observed to increase the risk of major congenital malformations, safety concerns have been raised ...