Metformin Versus Standard of Care Treatment in Pregnant Women With Prediabetes

Prediabetes; Complicating Pregnancy Clinical Trial

Official title:

Metformin Versus Standard of Care Treatment in Pregnant Women With Prediabetes: A Randomized Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04523363
• Other study ID #: H00021261
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: June 1, 2025
• Est. completion date: June 30, 2026

Study information

• Verified date: April 2024
• Source: University of Massachusetts, Worcester
• Contact: Gianna L Wilkie, MD
• Phone: 508-334-4067
• Email: Gianna.Wilkie[@]umassmemorial.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess if metformin reduces adverse outcomes associated with prediabetes in pregnancy. Our hypothesis is that pregnant women with prediabetes who are treated with metformin will show a greater reduction in large for gestational age infants at birth compared to women treated with the standard of care.

Description:

Women in pregnancy are routinely screened for diabetes in the first trimester and those who fall into the prediabetes category by hemoglobin A1c level of 5.7 to 6.4%, fasting plasma glucose of greater than or equal to 100 to 125, or oral glucose tolerance test of greater than or equal to 140 to less than 200 before 14 weeks gestation will be approached for consent in our randomized trial.

Once consent is obtained, the subjects will be randomized 1:1 into two parallel groups, the metformin treatment group and the standard of care treatment group (routine prenatal care). A random number generator will allocate the participants to the study groups.

Women taking metformin will continue twice daily dosing for the duration of their pregnancy after randomization. Those in the standard of care group will receive routine prenatal care. Both groups will undergo routine gestational diabetes testing by 28 weeks. Obstetric, maternal, and neonatal outcomes will then be assessed of both groups until the 6 week postpartum visit.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 240
• Est. completion date: June 30, 2026
• Est. primary completion date: June 30, 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Pregnant women with hemoglobin A1c of 5.7 to 6.4%, fasting plasma glucose of greater than or equal to 100 to 125, or oral glucose tolerance test of greater than or equal to 140 to less than 200 before 14 weeks gestation

• Pregnancy and delivery care obtained at University of Massachusetts (UMass) Memorial Medical Center

• Patients able to provide written informed consent

Exclusion Criteria:

• Pre-existing diabetes diagnosis as assessed at visit in the first trimester by history or by laboratory evaluation as listed above

• Presence of contra-indication to metformin (liver, renal, or heart failure) or sensitivity to metformin

• Participants who are under the age of 18

• Multiple Pregnancy

• Patients already taking metformin for other indications

• Fetal defect noted on early dating ultrasound

• Miscarriage before randomization

Related Conditions & MeSH terms

• Glucose Intolerance
• Prediabetes; Complicating Pregnancy
• Prediabetic State
• Pregnancy Complications

Intervention

Drug:
• Metformin
Maximum dosage of 500 mg tablets 2 times a day (with each meal)

Locations

Country	Name	City	State
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Gianna Wilkie

Country where clinical trial is conducted

United States, 

References & Publications (6)

Chen L, Pocobelli G, Yu O, Shortreed SM, Osmundson SS, Fuller S, Wartko PD, Mcculloch D, Warwick S, Newton KM, Dublin S. Early Pregnancy Hemoglobin A1C and Pregnancy Outcomes: A Population-Based Study. Am J Perinatol. 2019 Aug;36(10):1045-1053. doi: 10.1055/s-0038-1675619. Epub 2018 Nov 30. — View Citation

Lawrence JM, Contreras R, Chen W, Sacks DA. Trends in the prevalence of preexisting diabetes and gestational diabetes mellitus among a racially/ethnically diverse population of pregnant women, 1999-2005. Diabetes Care. 2008 May;31(5):899-904. doi: 10.2337/dc07-2345. Epub 2008 Jan 25. — View Citation

Lee AM, Fermin CR, Filipp SL, Gurka MJ, DeBoer MD. Examining trends in prediabetes and its relationship with the metabolic syndrome in US adolescents, 1999-2014. Acta Diabetol. 2017 Apr;54(4):373-381. doi: 10.1007/s00592-016-0958-6. Epub 2017 Jan 9. — View Citation

Peterson C, Grosse SD, Li R, Sharma AJ, Razzaghi H, Herman WH, Gilboa SM. Preventable health and cost burden of adverse birth outcomes associated with pregestational diabetes in the United States. Am J Obstet Gynecol. 2015 Jan;212(1):74.e1-9. doi: 10.1016/j.ajog.2014.09.009. Epub 2014 Oct 28. — View Citation

Professional Practice Committee for the Standards of Medical Care in Diabetes-2016. Diabetes Care. 2016 Jan;39 Suppl 1:S107-8. doi: 10.2337/dc16-S018. No abstract available. — View Citation

Temple R, Murphy H. Type 2 diabetes in pregnancy - An increasing problem. Best Pract Res Clin Endocrinol Metab. 2010 Aug;24(4):591-603. doi: 10.1016/j.beem.2010.05.011. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Birth Weight	Used to determine large for gestational age status	At Birth
Secondary	Number of Participants needing Cesarean Section	Number of Participants with Cesarean Section	At Delivery
Secondary	Number of Participants with Postpartum Hemorrhage	Estimated or quantitative blood loss greater than 1000 mL	At Delivery
Secondary	Number of Participants with Development of Pregnancy Induced Hypertension	Blood pressure, serum laboratory analysis, and urine protein would be assessed for diagnosis	Through study completion, starting at 14 weeks until delivery
Secondary	Development of Gestational Diabetes	A glucose tolerance test would be conducted at 28 weeks of pregnancy to diagnose diabetes	Assessed at 28 weeks of pregnancy
Secondary	Maternal Weight Gain in Pregnancy		At enrollment and last prenatal visit, starting at 14 weeks until delivery
Secondary	Pregnancy Outcome	Number of Participants with Stillbirth, livebirth, pregnancy loss	Through study completion, starting at 14 weeks until delivery
Secondary	Number of Participants with Preterm birth	Less than 37 week delivery	At delivery
Secondary	Neonatal Intensive Care Unit Admission	Admission to level 2 or greater neonatal ICU and length of stay	At delivery and within first 2 days of life
Secondary	Apgar Score at Birth	<6 at 1 and 5 minutes	At delivery
Secondary	Number of Participants with Neonatal Birth Trauma	Brachial plexus injury	At Delivery
Secondary	Number of Participants with Shoulder Dystocia		At Delivery
Secondary	Number of Participants with Neonatal Hypoglycemia		Within first 2 days of life
Secondary	Number of Participants with Neonatal Respiratory Distress	Requiring 2 or more hours of respiratory support or oxygen with associated diagnosis	At Delivery
Secondary	Number of Participants with Neonatal Hyperbilirubinemia	Requiring phototherapy	Within first 2 days of life
Secondary	Number of Participants requiring Neonatal Intubation		At Delivery
Secondary	Neonatal Cooling	Need for neonatal cooling within first 48 hours of life	Within first 2 days of life
Secondary	Umbilical Cord Blood Level of C-peptide		At Birth
Secondary	Umbilical Cord Blood Level of Leptin		At Birth
Secondary	Umbilical Cord Blood Level of Insulin		At Birth
Secondary	Placental Pathology	Assessing for malperfusion pathology	At Birth