RCT Metformin for Reduction of Gestational Diabetes Mellitus Effects

NCT02980276 | Completed Phase 3 Results DMC

• 1 other identifier: NUIG-2016-01
• Study Type: interventional
• Target: 535
• Locations: 1 country
• Sites: 2

Brief 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 morbidities and, d) cost of treatment for women with Gestational Diabetes Mellitus.

Conditions

Gestational Diabetes

Keywords

Gestational Diabetes; Diabetes; Pregnancy

Outcome Measures

Primary Outcomes (2)

• 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.

  Enrolment through delivery, an average of 16 weeks.

• Insulation of Insulin

  Initiation of insulin treatment at any time up to delivery.

  Enrolment through delivery, an average of 16 weeks.

Secondary Outcomes (32)

• Time to Insulin Initiation

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

• Insulin Initiated

  Enrolment through delivery, an average of 16 weeks.

• Fasting Hyperglycemia

  Measured at 32 and 38 weeks' gestation.

• Insulin Dose Required

  Enrolment through delivery, an average of 16 weeks.

• Gestational Weight Gain

  Enrolment through delivery, an average of 16 weeks.

Study Arms (2)

Treatment

ACTIVE COMPARATOR

Participants 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).

Drug: Metformin Hydrochloride

Control

PLACEBO COMPARATOR

Participants 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.

Other: Placebo

Interventions

Metformin Hydrochloride DRUG

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.

Treatment

Placebo OTHER

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.

Control

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National University of Ireland, Galway, Ireland: lead
• Health Research Board, Ireland: collaborator
• HRB Clinical Research Facility Galway: collaborator
• University College Hospital Galway: collaborator
• Portiuncula University Hospital: collaborator
• University Hospital of Limerick: collaborator
• University Maternity Hospital Limerick: collaborator
• Clinical Research Support Unit, University of Limerick: collaborator

Study Sites (2)

Portiuncula University Hospital

Ballinasloe, Galway, Ireland

Location

University Hospital Galway

Galway, Ireland

Location

Related Publications (3)

• 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.

  PMID: 39215812 DERIVED

• 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.

  PMID: 37786390 DERIVED

• 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.

  PMID: 36131291 DERIVED

MeSH Terms

Conditions

Diabetes, Gestational; Diabetes Mellitus

Interventions

Metformin

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Professor Fidelma Dunne
• Organization: University of Galway

fidelma.f.dunne@universityofgalway.ie

+35391492117

Study Officials

• Prof. Fidelma Dunne

  National University of Ireland, Galway, Ireland

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Fidelma Dunne

Study Record Dates

• First Submitted: November 9, 2016
• First Posted: December 2, 2016
• Study Start: June 6, 2017
• Primary Completion: January 12, 2023
• Study Completion: April 13, 2023
• Last Updated: March 17, 2025
• Results First Posted: March 17, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

IE (2)