Glyburide and Metformin for Gestational Diabetes Mellitus (GDM) (GDM)

May 7, 2026 updated by: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Glyburide and Metformin for Gestational Diabetes Mellitus

This is a pharmacokinetic and pharmacodynamic study evaluating glyburide, metformin, and combination treatment for gestational diabetes mellitus.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Gestational diabetes mellitus (GDM) is a common complication of pregnancy. Multiple treatment regimens are currently used for the management of GDM. Following failure of diet therapy, insulin, glyburide and metformin are all used in the treatment of GDM with the oral medications providing comparable outcomes with insulin but easier route of administration and schedule. The proposed work will evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of glyburide and metformin alone and in combination in order to lay the foundation in establishing dosage and response information that could be utilized in designing a phase III randomized trial that will ultimately evaluate GDM treatment optimization.

Study Type

Interventional

Enrollment (Actual)

177

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University School of Medicine
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh
    • Texas
      • Galveston, Texas, United States, 77555
        • University of Texas Medical Branch
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 41 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

Gestational Diabetes Subject Selection

  1. Pregnant women (singleton pregnancy)
  2. Gestational diabetes mellitus
  3. Able to give written informed consent
  4. Drug treatment is required for GDM

  5. Gestational age 20-32 weeks

    • Gestational diabetes diagnosis must occur after 20 weeks and prior to 32 weeks gestation
    • Randomization and treatment initiation must occur no later than 32 weeks gestation
  6. Willing to avoid ethanol
  7. 18-45 years of age

Type 2 Diabetes Mellitus Subject Selection

  1. Able to give written informed consent
  2. New diagnosis of type 2 diabetes mellitus
  3. Plan to receive metformin for treatment of type 2 diabetes mellitus
  4. 18-45 years of age
  5. Female
  6. Negative pregnancy test
  7. Hemoglobin A1C > 7%

Healthy Pregnant Women

  1. Able to give written informed consent
  2. Pregnant women (singleton)
  3. Normal 1-hour glucose tolerance test
  4. 20-32 weeks gestation
  5. 18-45 years of age

Neonates: All the infants of the pregnant women participating in this study will be included

Exclusion Criteria:

Women with GDM and T2DM

  1. Women taking medications expected to interact with glyburide, metformin or alter blood glucose concentrations
  2. Serum creatinine > 1.2 mg/dL
  3. Hematocrit < 28%
  4. Allergy to glyburide, metformin or sulfa
  5. Significant hepatic disease
  6. Congestive heart failure or history of MI
  7. Moderate to severe pulmonary disease
  8. Adrenal or pituitary insufficiency

Healthy Pregnant Women

  1. Receiving any hypoglycemic agents
  2. Receiving corticosteroids
  3. Known kidney, liver, heart, pulmonary, adrenal or pituitary disease
  4. Hematocrit < 28%

Neonates

  1. Infants that are not viable or too ill for blood sample collection will be included for clinical outcomes data collection, but will be excluded from other research activities.
  2. Infants < 1.5 kg will be included for clinical outcomes data collection, but will be excluded from blood sample collection.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: GDM Subjects
Women with GDM requiring treatment
Drug: Glyburide
Women with GDM who require treatment will be given glyburide 2.5 mg. Medication will be given at least twice daily and equal doses will be given for each dosing time for the 3 days prior to the pharmacokinetic study day.
Drug: Metformin
Women with GDM requiring treatment will be given metformin 500 mg. Medication will be administered at least twice daily and equal doses will be given for each dosing time for the 3 days prior to the pharmacokinetic study day.
Drug: Glyburide-Metformin combination
Women with GDM requiring treatment will be given glyburide 2.5 mg with metformin 500 mg. Medications will be administered at least twice daily and equal doses will be given for each dosing time 3 days prior to the pharmacokinetic study day.
No Intervention: Non-pregnant Type 2 Diabetes Milletus Subjects
Non-pregnant women with Type 2 diabetes mellitus who plan to use metformin treatment
No Intervention: Healthy Pregnant Women
Healthy pregnant women with normal 1-hour glucose tolerance test

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Study drug dosage in pregnancy
Time Frame: Completion of data collection (4-5mnths on average in GDM and healthy pregnant women and max of 6 months in newly diagnosed T2DMs)
(1) Determination of metformin dosage in pregnancy needed to produce comparable concentrations to the approved dosage range in non-pregnant women. (2)To compare metformin apparent oral clearance in pregnant and non-pregnant women. (3)To evaluate the effect of GLY monotherapy, MET monotherapy, and GLY-MET combination on insulin sensitivity, beta-cell responsivity index and disposition index (response vectors) describing the mechanism and magnitude of effect.
Completion of data collection (4-5mnths on average in GDM and healthy pregnant women and max of 6 months in newly diagnosed T2DMs)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine GLY and MET PK parameters
Time Frame: Conclusion of data collection (up to 6 months)
Determining GLY & MET PK parameters, including AUC, max concentration, time to max & min concentrations, oral clearance, half-life, oral volume of distribution, umbilical cord plasma concentrations; correlation between CYP2C9, CYP3A5, BCRP, OATP2B1 genotypes & GLY PK/PD; GLY & MET PD parameters, including derived parameters from PK/PD modeling for pregnant & nonpregnant subjects; duration of initiation of treatment to glycemic control; effects of GDM & glycemic control on maternal & umbilical cord EPC cells & sFLT concentrations; GLY & MET half-life in neonates; efficacy & safety data.
Conclusion of data collection (up to 6 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborators

University of Pittsburgh
University of Washington
University of Texas
Indiana University
RTI International

Investigators

  • Principal Investigator: Steve Caritis, MD, University of Pittsburgh
  • Principal Investigator: Mary F. Hebert, PharmD, FCCP, University of Washington
  • Principal Investigator: Gary DV Hankins, MD, University of Texas
  • Principal Investigator: David Flockhart, MD, PhD, Indiana University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2011

Primary Completion (Actual)

February 28, 2015

Study Completion (Actual)

February 28, 2015

Study Registration Dates

First Submitted

March 22, 2011

First Submitted That Met QC Criteria

April 4, 2011

First Posted (Estimated)

April 5, 2011

Study Record Updates

Last Update Posted (Actual)

May 11, 2026

Last Update Submitted That Met QC Criteria

May 7, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 820

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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