RCT Metformin for Reduction of Gestational Diabetes Mellitus Effects

National University of Ireland, Galway, Ireland535 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

535

Conditions

Gestational Diabetes

Interventions

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.

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 50 Years

Medical Language ↔ Plain English

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

Locations (2)

Portiuncula University Hospital

Ballinasloe, Galway, Ireland

University Hospital Galway

Galway, Ireland

Outcomes

Primary Outcomes

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.

Time frame: Enrolment through delivery, an average of 16 weeks.

Insulation of Insulin

Initiation of insulin treatment at any time up to delivery.

Time frame: Enrolment through delivery, an average of 16 weeks.

Secondary Outcomes

Time to Insulin Initiation

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

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

Insulin Initiated

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

Time frame: Enrolment through delivery, an average of 16 weeks.

Fasting Hyperglycemia

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

Time frame: Measured at 32 and 38 weeks' gestation.

Insulin Dose Required

Insulin dose required in any participant requiring insulin.

Time frame: Enrolment through delivery, an average of 16 weeks.

Gestational Weight Gain

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

Time frame: Enrolment through delivery, an average of 16 weeks.

Data from ClinicalTrials.gov

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