A Randomized Placebo Controlled Trial of the Effectiveness of Metformin in Addition to Usual Care in the Reduction of Gestational Diabetes Mellitus Effects

Phase 3

Completed

• Conditions: Gestational Diabetes
• Interventions: Other: Placebo; Drug: Metformin Hydrochloride

• Registration Number: NCT02980276
• Lead Sponsor: National University of Ireland, Galway, Ireland

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-11-09
• Study First Submitted QC: 2016-11-29
• Study First Posted: 2016-12-02
• Study Start: 2017-06-06
• Primary Completion: 2023-01-12
• Study Completion: 2023-04-13
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-11
• Last Update Posted: 2023-08-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 535

Inclusion Criteria

1. Willing and able to provide written informed consent
2. Participants aged 18-50
3. Pregnancy gestation up to 28 weeks (+ 6 days) confirmed by positive pregnancy test
4. Singleton pregnancy as determined by scan
5. 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
6. Resident in the locality and intending to deliver within the trial site

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Exclusion Criteria

1. Participants who have an established diagnosis of diabetes (Type 1, Type 2, Monogenic or secondary)
2. Participants with a fasting glucose > 7mmol/l or a 2h value > 11.1 mmol/l
3. Multiple pregnancies (twins, triplets etc.) as determined by scan
4. Known intolerance to metformin
5. 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
6. Major congenital malformations or an abnormally deemed unsuitable for metformin by the site PI or attending consultant
7. 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)
8. Known gestational hypertension or pre-eclampsia or ruptured membranes
9. Participants who have a history of drug or alcohol use that, in the opinion of the investigator, would interfere with adherence to study requirements
10. Participants with significant gastrointestinal problems such as severe vomiting, Crohn's disease or colitis which will inadvertently affect absorption of the study drug
11. Participants with congestive heart failure or history of congestive heart failure
12. Participants with serious mental illness which would affect adherence to study medication or compliance with study protocol in the opinion of the investigator
13. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	Placebo	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.
Treatment	Metformin Hydrochloride	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).

Primary Outcome Measures

Name	Time	Method
Insulin Initiation/Fasting Glucose	Change from Gestational Weeks 32 and 38	The primary efficacy outcome is a composite of: * Insulin initiation (Yes/No); * Fasting glucose value \</=5.1 mmol/l and \>5.1 mmol/l

Secondary Outcome Measures

Name	Time	Method
Post-partum BMI	12 weeks post-partum	Post-partum BMI in kg/m2 in participants between groups
Mode of Delivery	Delivery	Mode of delivery (e.g. vaginal, cesarean)
Postpartum glucose status, insulin resistance, and metabolic syndrome	12 weeks post-partum	Number of women with abnormal glucose values/insulin resistance/metabolic syndrome
Infant Birth Weight	Delivery	Weight in kg at birth
Neonatal morbidities	Delivery	Number of neonates with respiratory distress, jaundice, congenital anomalies, Apgar score, need for neonatal care unit
Quality of Life (EQ5D-5L)	Treatment week 12	Quality of Life determined by EQ5D-5L Questionnaire
Time of Delivery	Delivery	Gestational weeks at delivery
Treatment Acceptability	4 weeks post-partum	Treatment acceptability determined by Diabetes Treatment Satisfaction Questionnaire (DTSQ) and Rowan Questionnaire
Time to Insulin Initiation and Insulin Dose Required	Time to Insulin Initiation, from date of randomization until the date delivery, assessed up to 40 weeks	Time to Insulin Initiation, from date of randomization until the date delivery, assessed up to 40 weeks
Neonatal hypoglycaemia	12 weeks post-partum	Number of neonates with glucose \<2.6mmol/l
Maternal Morbidity at Delivery	Delivery	Number of women with maternal morbidity at delivery that is related to treatment (e.g. hypertensive disorders, antepartum/postpartum haemorrhage, polyhydramnios)
Neonatal height and head circumference at delivery	Delivery	Height in cm Head circumference in cm
Post partum waist circumference	12 weeks post partum	waist circumference in cm in participants between groups
Gestational weight gain	Change in weight from 24 weeks gestation until last visit before delivery	Change in weight (kg) from 24 weeks gestation until last visit before delivery

Trial Locations

Locations (2)

Portiuncula University Hospital; 🇮🇪 Ballinasloe, Galway, Ireland

University Hospital Galway; 🇮🇪 Galway, Ireland