Gestational Diabetes MellitusPhase 1/2GDMNCT01329016
Glyburide and Metformin for Gestational Diabetes Mellitus (GDM)
A Phase 1/2 study testing Glyburide, Metformin and Glyburide-Metformin combination in people with Gestational Diabetes Mellitus, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 4 sites in United States.
Trial summary
This is a pharmacokinetic and pharmacodynamic study evaluating glyburide, metformin, and combination treatment for gestational diabetes mellitus. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Gestational Diabetes Mellitus
- What is being tested?
- Glyburide, Metformin and Glyburide-Metformin combination
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 177 participants
- Where
- 4 sitesUnited States
- Study dates
- Jul 2011to 28 Feb 2015
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Gestational Diabetes Subject Selection
- Pregnant women (singleton pregnancy)
- Gestational diabetes mellitus
- Able to give written informed consent
- Drug treatment is required for GDM
- Gestational age 20-32 weeks
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- 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
- Willing to avoid ethanol
- 18-45 years of age
- Type 2 Diabetes Mellitus Subject Selection
- Able to give written informed consent
- New diagnosis of type 2 diabetes mellitus
- Plan to receive metformin for treatment of type 2 diabetes mellitus
- 18-45 years of age
- Female
- Negative pregnancy test
- Hemoglobin A1C > 7%
- Healthy Pregnant Women
- Able to give written informed consent
- Pregnant women (singleton)
- Normal 1-hour glucose tolerance test
- 20-32 weeks gestation
- 18-45 years of age
- Neonates: All the infants of the pregnant women participating in this study will be included
Who cannot join
- Women with GDM and T2DM
- Women taking medications expected to interact with glyburide, metformin or alter blood glucose concentrations
- Serum creatinine > 1.2 mg/dL
- Hematocrit < 28%
- Allergy to glyburide, metformin or sulfa
- Significant hepatic disease
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- Congestive heart failure or history of MI
- Moderate to severe pulmonary disease
- Adrenal or pituitary insufficiency
- Healthy Pregnant Women
- Receiving any hypoglycemic agents
- Receiving corticosteroids
- Known kidney, liver, heart, pulmonary, adrenal or pituitary disease
- Hematocrit < 28%
- Neonates
- 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.
- Infants < 1.5 kg will be included for clinical outcomes data collection, but will be excluded from blood sample collection.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Texas Medical Branch
Galveston, Texas, 77555
Indiana University School of Medicine
Indianapolis, Indiana, 46202
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
University of Washington
Seattle, Washington, 98195
About this study
Official title: Glyburide and Metformin for Gestational Diabetes Mellitus
This is a pharmacokinetic and pharmacodynamic study evaluating glyburide, metformin, and combination treatment for gestational diabetes mellitus.
Read the 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.
- Conditions
- Gestational Diabetes Mellitus
- Being tested
- Glyburide, Metformin, Glyburide-Metformin combination
- Keywords
- Pregnancy, Glyburide, Metformin, Pharmacokinetics, Pharmacodynamics
- Medical subject headings
- Diabetes, Gestational
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlyburideDrug
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.
MetforminDrug
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.
Glyburide-Metformin combinationDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| GDM Subjects | Active comparator | Women with GDM requiring treatment Receives: Drug: Glyburide; Drug: Metformin; Drug: Glyburide-Metformin combination |
| Non-pregnant Type 2 Diabetes Milletus Subjects | No intervention | Non-pregnant women with Type 2 diabetes mellitus who plan to use metformin treatment |
| Healthy Pregnant Women | No intervention | Healthy pregnant women with normal 1-hour glucose tolerance test |
What is being measured
The primary outcome is the main question the study is designed to answer.
Study drug dosage in pregnancy
(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.
Measured: Completion of data collection (4-5mnths on average in GDM and healthy pregnant women and max of 6 months in newly diagnosed T2DMs)
Secondary outcomes (1)
Determine GLY and MET PK parameters
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.
Measured: Conclusion of data collection (up to 6 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2011 (estimated)
- Study startJul 2011
- Primary completion28 Feb 2015
- Study completion28 Feb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Gestational Diabetes MellitusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 177 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
- Collaborators
- University of Washington, University of Pittsburgh, University of Texas, Indiana University, RTI International
- Responsible party
- Sponsor
- Investigators
- Mary F. Hebert, PharmD, FCCP, Principal investigator, University of WashingtonSteve Caritis, MD, Principal investigator, University of PittsburghGary DV Hankins, MD, Principal investigator, University of TexasDavid Flockhart, MD, PhD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01329016
- Sponsor's protocol ID
- 820
- Acronym
- GDM
- Status last verified
- May 2026
- First submitted
- 22 Mar 2011
- Last updated
- 11 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Liao MZ, Flood Nichols SK, Ahmed M, Clark S, Hankins GD, Caritis S, Venkataramanan R, Haas D, Quinney SK, Haneline LS, Tita AT, Manuck T, Wang J, Thummel KE, Brown LM, Ren Z, Easterling TR, Hebert MF. Effects of Pregnancy on the Pharmacokinetics of Metformin. Drug Metab Dispos. 2020 Apr;48(4):264-271. doi: 10.1124/dmd.119.088435. Epub 2020 Jan 24.
PubMed 31980499Shuster DL, Shireman LM, Ma X, Shen DD, Flood Nichols SK, Ahmed MS, Clark S, Caritis S, Venkataramanan R, Haas DM, Quinney SK, Haneline LS, Tita AT, Manuck TA, Thummel KE, Brown LM, Ren Z, Brown Z, Easterling TR, Hebert MF. Pharmacodynamics of Glyburide, Metformin, and Glyburide/Metformin Combination Therapy in the Treatment of Gestational Diabetes Mellitus. Clin Pharmacol Ther. 2020 Jun;107(6):1362-1372. doi: 10.1002/cpt.1749. Epub 2020 Jan 25.
PubMed 31869430Shuster DL, Shireman LM, Ma X, Shen DD, Flood Nichols SK, Ahmed MS, Clark S, Caritis S, Venkataramanan R, Haas DM, Quinney SK, Haneline LS, Tita AT, Manuck TA, Thummel KE, Morris Brown L, Ren Z, Brown Z, Easterling TR, Hebert MF. Pharmacodynamics of Metformin in Pregnant Women With Gestational Diabetes Mellitus and Nonpregnant Women With Type 2 Diabetes Mellitus. J Clin Pharmacol. 2020 Apr;60(4):540-549. doi: 10.1002/jcph.1549. Epub 2019 Nov 19.
PubMed 31742716
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glyburide and Metformin for Gestational Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT01329016
- Acronym / sponsor ID
- GDM / 820
- Conditions
- Gestational Diabetes Mellitus
- Keywords
- Pregnancy, Glyburide, Metformin, Pharmacokinetics, Pharmacodynamics
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 177 participants (actual)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Collaborators
- University of Washington, University of Pittsburgh, University of Texas, Indiana University, RTI International
- Study start
- Jul 2011
- Primary completion
- 28 Feb 2015 (actual)
- Study completion
- 28 Feb 2015 (actual)
- First posted
- 5 Apr 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a pharmacokinetic and pharmacodynamic study evaluating glyburide, metformin, and combination treatment for gestational diabetes mellitus.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| GDM Subjects | Active comparator | Drug: Glyburide, Drug: Metformin, Drug: Glyburide-Metformin combinationWomen with GDM requiring treatment |
| Non-pregnant Type 2 Diabetes Milletus Subjects | No intervention | –Non-pregnant women with Type 2 diabetes mellitus who plan to use metformin treatment |
| Healthy Pregnant Women | No intervention | –Healthy pregnant women with normal 1-hour glucose tolerance test |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (25 listed)
- Gestational Diabetes Subject Selection
- Pregnant women (singleton pregnancy)
- Gestational diabetes mellitus
- Able to give written informed consent
- Drug treatment is required for GDM
Key exclusion criteria (17 listed)
- Women with GDM and T2DM
- Women taking medications expected to interact with glyburide, metformin or alter blood glucose concentrations
- Serum creatinine > 1.2 mg/dL
- Hematocrit < 28%
- Allergy to glyburide, metformin or sulfa
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GlyburideWomen 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 | GDM Subjects |
| MetforminWomen 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 | GDM Subjects |
| Glyburide-Metformin combinationWomen 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. | Drug | GDM Subjects |
Primary outcome
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.
1 secondary outcome
Determine GLY and MET PK parameters
Time frame: Conclusion of data collection (up to 6 months)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2026.
- Results publication: PubMed 31980499Liao MZ, Flood Nichols SK, Ahmed M, Clark S, Hankins GD, Caritis S, Venkataramanan R, Haas D, Quinney SK, Haneline LS, Tita AT, Manuck T, Wang J, Thummel KE, Brown LM, Ren Z, Easterling TR, Hebert MF. Effects of Pregnancy on the Pharmacokinetics of Metformin. Drug Metab Dispos. 2020 Apr;48(4):264-271. doi: 10.1124/dmd.119.088435. Epub 2020 Jan 24.
- Results publication: PubMed 31869430Shuster DL, Shireman LM, Ma X, Shen DD, Flood Nichols SK, Ahmed MS, Clark S, Caritis S, Venkataramanan R, Haas DM, Quinney SK, Haneline LS, Tita AT, Manuck TA, Thummel KE, Brown LM, Ren Z, Brown Z, Easterling TR, Hebert MF. Pharmacodynamics of Glyburide, Metformin, and Glyburide/Metformin Combination Therapy in the Treatment of Gestational Diabetes Mellitus. Clin Pharmacol Ther. 2020 Jun;107(6):1362-1372. doi: 10.1002/cpt.1749. Epub 2020 Jan 25.
- Results publication: PubMed 31742716Shuster DL, Shireman LM, Ma X, Shen DD, Flood Nichols SK, Ahmed MS, Clark S, Caritis S, Venkataramanan R, Haas DM, Quinney SK, Haneline LS, Tita AT, Manuck TA, Thummel KE, Morris Brown L, Ren Z, Brown Z, Easterling TR, Hebert MF. Pharmacodynamics of Metformin in Pregnant Women With Gestational Diabetes Mellitus and Nonpregnant Women With Type 2 Diabetes Mellitus. J Clin Pharmacol. 2020 Apr;60(4):540-549. doi: 10.1002/jcph.1549. Epub 2019 Nov 19.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mary F. Hebert, PharmD, FCCP principal investigator
University of Washington
Steve Caritis, MD principal investigator
University of Pittsburgh
Gary DV Hankins, MD principal investigator
University of Texas
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Glyburide, Metformin and Glyburide-Metformin combination in people with Gestational Diabetes Mellitus, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01329016, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2026.