RCT Metformin for Reduction of Gestational Diabetes Melli... | NCT02980276

NCT02980276

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
Health Research Board, Ireland	OTHER
HRB Clinical Research Facility Galway	OTHER
University College Hospital Galway	OTHER
Portiuncula University Hospital

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

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

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Name	Affiliation	Role
Prof. Fidelma Dunne	National University of Ireland, Galway, Ireland	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Portiuncula University Hospital		Ballinasloe	Galway		Ireland
University Hospital Galway

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
39215812	Derived	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.
37786390

Arm/Group Information

ID	Title	Description
FG000	Treatment	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). 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.
FG001	Control	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. 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.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG000268 subjects FG001267 subjects
Included in Analysis of Primary Outcome	262 participated in study until delivery. 264 participants included in analysis of primary outcome	FG000264 subjects FG001262 subjects
COMPLETED	Completed all study visits.	FG000235 subjects FG001240 subjects
NOT COMPLETED		FG00033 subjects FG00127 subjects

Type	Comment	Reasons
Withdrawal by Subject		FG0004 subjects FG0014 subjects
Physician Decision		FG0000 subjects FG001

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Treatment	Participants randomised to the treatment arm received 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).

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical	Age range in years at time of randomisation.

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Population of pregnancies followed up until delivery. 268 were randomised to Treatment Group, of whom 264 received Metformin as randomised. Two participants delivered outside the country; delivery and neonatal information was available for the remaining 262 participants. Among those randomised to Treatment Group, 264 Pregnancies were included in the Primary Outcome Analysis. All 262 patients randomised to placebo were followed until delivery and included in Primary Outome Analysis.

Posted

Count of Participants

Participants

Enrolment through delivery, an average of 16 weeks.

ID	Title	Description
OG000	Treatment	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). 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.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Treatment - Mother	Women randomised to the metformin group received 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.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 2, 2019	Sep 6, 2024	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Mar 21, 2023	Sep 6, 2024	SAP_001.pdf

ID	Term
D016640	Diabetes, Gestational
D003920	Diabetes Mellitus

ID	Term
D011248	Pregnancy Complications
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D044882	Glucose Metabolism Disorders

ID	Term
D001645	Biguanides
D006146	Guanidines
D000578	Amidines
D009930	Organic Chemicals