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Gestational DiabetesPhase 3EMERGENCT02980276

RCT Metformin for Reduction of Gestational Diabetes Mellitus Effects

A Phase 3 study testing Metformin Hydrochloride in people with Gestational Diabetes, run by National University of Ireland, Galway, Ireland at 2 sites in Ireland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The overall objective of the EMERGE trial is to determine whether metformin + usual care, compared to placebo + usual care (introduced at the time of initial diagnosis of GDM), reduces a) the need for insulin use, or hyperglycemia (primary outcome measure); b) excessive maternal weight gain; c) maternal and neonatal… Read more about this study

Who is it for?
Ages 18 to 50 years, women only
Conditions the study is for
Gestational Diabetes
What is being tested?
Metformin Hydrochloride
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
535 participants
Where
2 sitesIreland
Study dates
6 Jun 2017to 13 Apr 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 50 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • Willing and able to provide written informed consent
  • Participants aged 18-50
  • Pregnancy gestation up to 28 weeks (+ 6 days) confirmed by positive pregnancy test
  • Singleton pregnancy as determined by scan
  • Positive diagnosis of Gestational Diabetes Mellitus on a Oral Glucose Tolerance Test (OGTT) according to the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria if any one of the following are achieved: i) Fasting glucose >/= 5.1mmol/l and <7mmol/l, or ii) 1 hour post glucose load of >/=10mmol/l, or iii) 2 hour post glucose load of >/=8.5 mmol/l and <11.1mmo/l
  • Resident in the locality and intending to deliver within the trial site

Who cannot join

  • Participants who have an established diagnosis of diabetes (Type 1, Type 2, Monogenic or secondary)
  • Participants with a fasting glucose > 7mmol/l or a 2h value > 11.1 mmol/l
  • Multiple pregnancies (twins, triplets etc.) as determined by scan
  • Known intolerance to metformin
  • Known contraindication to the use of metformin which include: i) renal insufficiency (defined as serum creatinine of greater than 130 µmol/L or creatinine clearance <60 ml/min), ii) moderate to severe liver dysfunction (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) greater than 3 times the upper limit of normal, iii) shock or sepsis, and iv) previous hypersensitivity to metformin
  • Major congenital malformations or an abnormally deemed unsuitable for metformin by the site PI or attending consultant
Show all 13Show fewer
  • Known small for gestational age (Small for gestational age (SGA) refers to foetal growth less than the 10th percentile (RCOG, 2014), or if foetal growth is deemed unsatisfactory by the treating obstetrician)
  • Known gestational hypertension or pre-eclampsia or ruptured membranes
  • Participants who have a history of drug or alcohol use that, in the opinion of the investigator, would interfere with adherence to study requirements
  • Participants with significant gastrointestinal problems such as severe vomiting, Crohn's disease or colitis which will inadvertently affect absorption of the study drug
  • Participants with congestive heart failure or history of congestive heart failure
  • Participants with serious mental illness which would affect adherence to study medication or compliance with study protocol in the opinion of the investigator
  • Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption

Trial locations and contacts

2 sites in 1 country.

Ireland2 sites
  • Portiuncula University Hospital

    Ballinasloe, Galway

  • University Hospital Galway

    Galway

Other trials in Ireland

About this study

Official title: A Randomised Placebo Controlled Trial of the Effectiveness of Early MEtformin in Addition to Usual Care in the Reduction of Gestational Diabetes Mellitus Effects (EMERGE)

The overall objective of the EMERGE trial is to determine whether metformin + usual care, compared to placebo + usual care (introduced at the time of initial diagnosis of GDM), reduces a) the need for insulin use, or hyperglycemia (primary outcome measure); b) excessive maternal weight gain; c) maternal and neonatal morbidities and, d) cost of treatment for women with Gestational Diabetes Mellitus.

Being tested
Metformin Hydrochloride, Placebo
Keywords
Gestational Diabetes, Diabetes, Pregnancy
Medical subject headings
Diabetes, Gestational, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Metformin HydrochlorideDrug

    Women randomised to the metformin group will receive metformin 500mg once daily, with the dose titrated upwards every 2 days over 10 days increasing to a maximum of 2500mg Metformin daily (5 tablets) or maximum tolerated dose, in addition to usual care (exercise and MNT), and taken until delivery.

  • PlaceboOther

    Women randomised to the placebo group will receive 1 placebo tablet once daily, with the dose titrated upwards every 2 days over 10 days increasing to a maximum of five placebo tablets daily, in addition to usual care (exercise and MNT), and taken until delivery.

Study groups in NCT02980276
Study groupRoleWhat they receive
TreatmentActive comparatorParticipants randomised to the treatment arm will receive active metformin in addition to standard care. Metformin tablets will be titrated according to a dosing schedule to achieve the pre-specified glucose targets. Tablets will be in 500mg doses and will commence at 1 tablet per day (500mg) increasing to a maximum of 5 tablets per day (2500mg).
Receives: Drug: Metformin Hydrochloride
ControlPlacebo comparatorParticipants randomised to the placebo arm will receive placebo in addition to standard care. Placebo will be titrated according to the dosing schedule to achieve the pre-specified glucose targets. Placebo tablets will commence at 1 tablet per day and will be increased to a maximum of 5 tablets per day over 10 days as with the treatment group.
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Primary Composite Outcome

    The primary efficacy outcome was achieved if any participant experienced:

    • Insulin initiation
    • Fasting glucose value >5.1 mmol/l at 32weeks or 38 weeks gestation.

    Measured: Enrolment through delivery, an average of 16 weeks.

  2. Insulation of Insulin

    Initiation of insulin treatment at any time up to delivery.

    Measured: Enrolment through delivery, an average of 16 weeks.

Secondary outcomes (32)
  1. Time to Insulin Initiation

    Time to Insulin Initiation, from date of randomization until the date of delivery.

    Measured: Time to Insulin Initiation, from date of randomization until the date of delivery, an average of 16 weeks..

  2. Insulin Initiated

    Whether or not insulin was initiated at any time during the study.

    Measured: Enrolment through delivery, an average of 16 weeks.

  3. Fasting Hyperglycemia

    Number of women with fasting hyperglycemia at 32wks or at 38wks gestation.

    Measured: Measured at 32 and 38 weeks' gestation.

  4. Insulin Dose Required

    Insulin dose required in any participant requiring insulin.

    Measured: Enrolment through delivery, an average of 16 weeks.

  5. Gestational Weight Gain

    Change in weight (kg) from randomization until last visit before delivery

    Measured: Enrolment through delivery, an average of 16 weeks.

  6. Postpartum Impaired Fasting Glucose

    Impaired fasting glucose at 12 weeks postpartum

    Measured: 12 weeks post-partum

  7. Postpartum Impaired Glucose Tolerance

    Measured: 12 weeks postpartum

  8. Postpartum Metabolic Syndrome

    Measured: 12 weeks postpartum

  9. Gestational Age at Delivery

    Measured: At delivery, an average of 16 weeks after enrolment

  10. Mode of Delivery - Cesarian Delivery

    Delivered by Cesarian section.

    Measured: At delivery, an average of 16 weeks after enrolment

  11. Mode of Delivery - Emergency Cesarian Section

    Among those having cesarian section, count of emergency procedures.

    Measured: At delivery, an average of 16 weeks after randomization.

  12. Mode of Delivery - Induced

    Labor induced.

    Measured: At time of labor, an average of 16 weeks after enrolment.

  13. Maternal Morbidity - Pregnancy-induced Hypertension

    Measured: From enrolment through 6 weeks postpartum, an average of 22 weeks.

  14. Maternal Morbidity - Pre-eclampsia

    Pre-eclampsia diagnosed during study participation

    Measured: Enrolment through 6 weeks postpartum, an average of 22 weeks.

  15. Maternal Morbidity - Antepartum Hemorrhage

    Any vaginal bleeding prior to delivery

    Measured: From enrolment through delivery, an average of 16 weeks.

  16. Maternal Morbidity - Postpartum Hemorrhage

    Measured: From delivery through 6 weeks postpartum.

  17. Birthweight

    Measured: At birth

  18. Neonatal Head Circumference

    Measured: At birth

  19. Neonatal Height

    Height in cm (crown-heel length)

    Measured: At birth

  20. Neonatal Abdominal Circumference

    Measured: At birth

  21. Neonatal Ponderal Index

    Ponderal index is calculated as 100 x weight(grams)/(crown-heel length).

    Measured: At birth

  22. Birth Weight >4000g

    Measured: At birth

  23. Birth Weight >90th Percentile

    Measured: At birth

  24. Birth Weight <2500g

    Measured: At birth

  25. Birth Weight <10th Percentile

    Measured: At birth

  26. Neonatal Morbidity - Need for NICU Care

    Measured: From birth until 6 weeks of life.

  27. Neonatal Morbidity - Preterm Birth

    Delivery at gestational age <37 weeks.

    Measured: At birth

  28. Neonatal Morbidity - Respiratory Distress Syndrome Requiring Respiratory Support

    Measured: From birth until 6 weeks of life.

  29. Neonatal Morbidity - Jaundice Requiring Phototherapy

    Measured: From birth until 6 weeks of life.

  30. Neonatal Morbidity - Major Congenital Anomalies

    Measured: From birth until 6 weeks of life.

  31. Neonatal Morbidity - Apgar Score <7 at 5 Minutes

    The Apgar score comprises five components: 1) color, 2) heart rate, 3) reflexes, 4) muscle tone, and 5) respiration, each of which is given a score of 0, 1, or 2.

    (for example see: https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2015/10/the-apgar-score#:~:text=The%20Apgar%20score%20comprises%20five,0%2C%201%2C%20or%202)

    Measured: At 5 minutes after birth

  32. Neonatal Morbidity - Neonatal Hypoglycemia

    serum glucose <2.6mmol/l on at least one occasion <60 minutes after delivery

    Measured: First hour of life.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Dec 2016 (estimated)
  2. Study start6 Jun 2017
  3. Primary completion12 Jan 2023
  4. Study completion13 Apr 2023

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
535 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02980276
Sponsor's protocol ID
NUIG-2016-01
Acronym
EMERGE
Status last verified
Mar 2025
First submitted
9 Nov 2016
Last updated
17 Mar 2025
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Aguilar Macias DA, Alvarez-Iglesias A, Ferguson JM, Egan AM, O'Shea PM, Devane D, Newman C, McEvoy RP, FitzGerald M, O'Donnell MJ, Dunne FF. Early Metformin Initiation and Glycemic Outcomes in Gestational Diabetes: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2026 Nov 2;9(11):e2635700. doi: 10.1001/jamanetworkopen.2026.35700.

    PubMed 42975901
  • Dunne F, Newman C, Alvarez-Iglesias A, O'Shea P, Devane D, Gillespie P, Egan A, O'Donnell M, Smyth A. Metformin and small for gestational age babies: findings of a randomised placebo-controlled clinical trial of metformin in gestational diabetes (EMERGE). Diabetologia. 2024 Dec;67(12):2660-2666. doi: 10.1007/s00125-024-06252-y. Epub 2024 Aug 31.

    PubMed 39215812
  • Dunne F, Newman C, Alvarez-Iglesias A, Ferguson J, Smyth A, Browne M, O'Shea P, Devane D, Gillespie P, Bogdanet D, Kgosidialwa O, Egan A, Finn Y, Gaffney G, Khattak A, O'Keeffe D, Liew A, O'Donnell M. Early Metformin in Gestational Diabetes: A Randomized Clinical Trial. JAMA. 2023 Oct 24;330(16):1547-1556. doi: 10.1001/jama.2023.19869.

    PubMed 37786390
  • Dunne F, Newman C, Devane D, Smyth A, Alvarez-Iglesias A, Gillespie P, Browne M, O'Donnell M. A randomised placebo-controlled trial of the effectiveness of early metformin in addition to usual care in the reduction of gestational diabetes mellitus effects (EMERGE): study protocol. Trials. 2022 Sep 21;23(1):795. doi: 10.1186/s13063-022-06694-y.

    PubMed 36131291

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Metformin Hydrochloride in people with Gestational Diabetes, run by National University of Ireland, Galway, Ireland at 2 sites in Ireland.

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 6 inclusion and 13 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 17 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Ireland. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Primary Composite Outcome (time frame: Enrolment through delivery, an average of 16 weeks.). The study lists 2 primary outcomes in all. 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 NCT02980276, which also lists 4 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 17 Mar 2025.

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