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

Gestational Diabetes Clinical Trial

— EMERGE  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02980276
• Other study ID #: NUIG-2016-01
• Status: Completed
• Phase: Phase 3
• Start date: June 6, 2017
• Est. completion date: April 13, 2023

Study information

• Verified date: August 2023
• Source: National University of Ireland, Galway, Ireland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 535
• Est. completion date: April 13, 2023
• Est. primary completion date: January 12, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes, Gestational
• Gestational Diabetes

Intervention

Drug:
• Metformin Hydrochloride
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.

Other:
• Placebo
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.

Locations

Country	Name	City	State
Ireland	Portiuncula University Hospital	Ballinasloe	Galway
Ireland	University Hospital Galway	Galway

Sponsors (8)

Lead Sponsor	Collaborator
National University of Ireland, Galway, Ireland	Clinical Research Support Unit, University of Limerick, Health Research Board, Ireland, HRB Clinical Research Facility Galway, Ireland, Portiuncula University Hospital, University College Hospital Galway, University Hospital of Limerick, University Maternity Hospital Limerick

Country where clinical trial is conducted

Ireland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cost effectiveness and budget impact of metformin treatment in addition to standard care		24 weeks gestation to 12 weeks post-partum
Primary	Insulin Initiation/Fasting Glucose	The primary efficacy outcome is a composite of: Insulin initiation (Yes/No); Fasting glucose value	Change from Gestational Weeks 32 and 38
Secondary	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
Secondary	Maternal Morbidity at Delivery	Number of women with maternal morbidity at delivery that is related to treatment (e.g. hypertensive disorders, antepartum/postpartum haemorrhage, polyhydramnios)	Delivery
Secondary	Mode of Delivery	Mode of delivery (e.g. vaginal, cesarean)	Delivery
Secondary	Time of Delivery	Gestational weeks at delivery	Delivery
Secondary	Postpartum glucose status, insulin resistance, and metabolic syndrome	Number of women with abnormal glucose values/insulin resistance/metabolic syndrome	12 weeks post-partum
Secondary	Post-partum BMI	Post-partum BMI in kg/m2 in participants between groups	12 weeks post-partum
Secondary	Infant Birth Weight	Weight in kg at birth	Delivery
Secondary	Neonatal height and head circumference at delivery	Height in cm Head circumference in cm	Delivery
Secondary	Neonatal morbidities	Number of neonates with respiratory distress, jaundice, congenital anomalies, Apgar score, need for neonatal care unit	Delivery
Secondary	Neonatal hypoglycaemia	Number of neonates with glucose <2.6mmol/l	Delivery
Secondary	Neonatal hypoglycaemia	Number of neonates with glucose <2.6mmol/l	12 weeks post-partum
Secondary	Treatment Acceptability	Treatment acceptability determined by Diabetes Treatment Satisfaction Questionnaire (DTSQ) and Rowan Questionnaire	4 weeks post-partum
Secondary	Quality of Life (EQ5D-5L)	Quality of Life determined by EQ5D-5L Questionnaire	Treatment week 12
Secondary	Post partum waist circumference	waist circumference in cm in participants between groups	12 weeks post partum
Secondary	Gestational weight gain	Change in weight (kg) from 24 weeks gestation until last visit before delivery	Change in weight from 24 weeks gestation until last visit before delivery