Preventing Recurrent Gestational Diabetes With Metformin

Study Overview
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Brief Summary
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Study Hypothesis: Intervention with metformin therapy early in pregnancy will prevent gestational diabetes mellitus recurring in previously affected pregnancies.

Detailed Description
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Gestational diabetes mellitus (GDM) is a common medical complication of pregnancy and is associated with increased risks to mother and baby. The incidence is increasing reflecting changing pre-gravid female demographics. Once one pregnancy is complicated by GDM, subsequent pregnancies are more likely to be affected by the same condition. This reported risk of recurrence is estimated to range between 35 and 80%, with non-caucasian ethnicity being the strongest predictor of GDM recurrence. Evidence regarding further predictors of recurrent GDM is conflicting and measures that might prevent recurrence need exploring. Metformin is commonly used in the treatment of established GDM and has been shown to reduce the incidence of GDM in the context of polycystic ovarian syndrome.

Official Title
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Preventing Recurrent Gestational Diabetes Mellitus With Early Metformin Intervention

Conditions
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Gestational Diabetes Mellitus

Intervention / Treatment
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* Drug: Metformin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Singleton pregnancy; 8-22 weeks gestation Previous pregnancy complicated by gestational diabetes Exclusion Criteria: Established pre-existing diabetes (including unrecognised diabetes defined as a fasting plasma glucose ≥ 7.0mmol/L and/ or HbA1c ≥ 48mmol/mol); Contraindications to metformin therapy (creatinine ≥ 130μmol/L/ alanine transaminase ≥ 2.0 x upper limit normal/ previous intolerance to metformin) Planned continued antenatal care/ delivery at centre not included in trial Planned fast for cultural/ religious reasons e.g. Ramadan

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention arm Metformin<br>Metformin (500mg tablets) to start at a dose of 500mg once daily with an increase of 500mg every five days until the maximum dose of 1000mg twice daily is reached. | Drug: Metformin<br> <br> |
| Placebo Comparator: Control arm placebo<br>Matched placebo tablets (500mg) to start at a dose of 500mg once daily with an increase of 500mg every five days until the maximum dose of 1000mg twice daily is reached. | Drug: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of Gestational Diabetes at any point during the course of pregnancy |  | From 12 weeks pregnancy until the onset of labour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maternal gestational weight gain |  | Difference between weight at 12 weeks gestation and 36 weeks gestation | 
| Requirement for insulin therapy |  | From 12 weeks gestation until 36 weeks gestation | 
| Postpartum glucose levels |  | 6 weeks postpartum | 
| Levels of maternal physical and psychological health as assessed by questionnaires |  | From 12 weeks gestation until 6 weeks postpartum | 
| Fetal birthweight and birthweight centile |  | At Birth | 
| Composite of neonatal outcomes (neonatal hypoglycaemia requiring treatment, respiratory distress syndrome requiring oxygen therapy/ continuous positive airway pressure, neonatal hyperbilirubinaemia requiring phototherapy). |  | At Birth | 
| Cost effectiveness of the intervention | Difference in requirement for medical services and unplanned hospital/ General Practitioner attendances between the two arms | From 12 weeks gestation until 6 weeks postpartum | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recurrent Gestational Diabetes Mellitus, Prevention, Metformin