Metformin Versus Standard of Care Treatment in Pregnant Women With Prediabetes

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Prediabetes; Complicating Pregnancy
• Intervention / Treatment: Drug: Metformin

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 240
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Gianna L Wilkie, MD; Phone Number: 508-334-4067; Email: Gianna.Wilkie@umassmemorial.org
• Study Contact Backup: Name: Heidi Leftwich, DO; Email: Heidi.Leftwich@umassmemorial.org

Study Locations

• United States
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • University of Massachusetts Memorial Medical Center
      • Contact: Gianna L Wilkie, MD; Phone Number: 508-334-4067; Email: Gianna.Wilkie@umassmemorial.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metformin; 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.	Drug: Metformin; Maximum dosage of 500 mg tablets 2 times a day (with each meal); Other Names: Glucophage
No Intervention: Standard of Care; Study subjects will be randomized to standard of care and receive routine prenatal care without further intervention for their prediabetes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Birth Weight	Used to determine large for gestational age status	At Birth

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants needing Cesarean Section	Number of Participants with Cesarean Section	At Delivery
Number of Participants with Postpartum Hemorrhage	Estimated or quantitative blood loss greater than 1000 mL	At Delivery
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
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
Maternal Weight Gain in Pregnancy		At enrollment and last prenatal visit, starting at 14 weeks until delivery
Pregnancy Outcome	Number of Participants with Stillbirth, livebirth, pregnancy loss	Through study completion, starting at 14 weeks until delivery
Number of Participants with Preterm birth	Less than 37 week delivery	At delivery
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
Apgar Score at Birth	<6 at 1 and 5 minutes	At delivery
Number of Participants with Neonatal Birth Trauma	Brachial plexus injury	At Delivery
Number of Participants with Shoulder Dystocia		At Delivery
Number of Participants with Neonatal Hypoglycemia		Within first 2 days of life
Number of Participants with Neonatal Respiratory Distress	Requiring 2 or more hours of respiratory support or oxygen with associated diagnosis	At Delivery
Number of Participants with Neonatal Hyperbilirubinemia	Requiring phototherapy	Within first 2 days of life
Number of Participants requiring Neonatal Intubation		At Delivery
Neonatal Cooling	Need for neonatal cooling within first 48 hours of life	Within first 2 days of life
Umbilical Cord Blood Level of C-peptide		At Birth
Umbilical Cord Blood Level of Leptin		At Birth
Umbilical Cord Blood Level of Insulin		At Birth
Placental Pathology	Assessing for malperfusion pathology	At Birth

Collaborators and Investigators

• Sponsor: Gianna Wilkie
• Investigators: Principal Investigator: Gianna L Wilkie, MD, UMass Memorial Health Care

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2025
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): June 30, 2026

Study Registration Dates

• First Submitted: August 18, 2020
• First Submitted That Met QC Criteria: August 20, 2020
• First Posted (Actual): August 21, 2020

Study Record Updates

• Last Update Posted (Actual): May 3, 2023
• Last Update Submitted That Met QC Criteria: May 2, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: pregnancy; metformin; prediabetes; maternal outcomes; neonatal outcomes
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hyperglycemia; Prediabetic State; Glucose Intolerance; Pregnancy Complications; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: H00021261

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No