Metformin in mild gestational diabetes mellitus: a double-blind placebo-controlled randomised trial

• Register: ISRCTN
• Last refreshed on: 7 November 2022
• Main ID: ISRCTN10845466
• Date of registration: 07/11/2017
• Prospective Registration: Yes
• Primary sponsor: University Malaya Medical Centre
• Public title: Metformin in mild gestational diabetes mellitus: a double-blind placebo-controlled randomised trial
• Scientific title: Metformin in Mild Gestational Diabetes Mellitus : a double-blind placebo-controlled randomised trial
• Date of first enrolment: 13/11/2017
• Target sample size: 106
• Recruitment status: Completed
• URL: https://www.isrctn.com/ISRCTN10845466
• Study type: Interventional
• Study design: Randomised double-blind placebo-controlled trial (Treatment)
• Phase: Not Specified

Countries of recruitment

Malaysia

Contacts

• Name: Min Ping Tew

Key inclusion & exclusion criteria

Inclusion criteria:
Current inclusion criteria as of 11/12/2017:
1. Aged 18 to 45 years
2. Singleton pregnancy
3. Gestational age at recruitment 16-30 weeks
4. Confirmed GDM: Fasting plasma glucose = 5.1 mmol/L and/or the 2-hour = 7.8 mmol/L by 75g OGTT
5. Normal 4-point blood sugar profile (BSP) in the preceding 2 weeks: fasting/pre-prandial = 5.3, post prandial 1 hour of = 7.8 or post prandial 2 hours of = 6.7 mmol/L
6. Not on any hypoglycaemic drug treatment

Previous inclusion criteria:
1. Aged 18 to 45 years
2. Singleton pregnancy
3. Gestational age at recruitment 16-30 weeks
4. Confirmed GDM: Fasting plasma glucose = 5.1 mmol/L and/or the 2-hour = 7.8 mmol/L by 75g OGTT = 16 weeks of pregnancy
5. Normal 4-point blood sugar profile (BSP) in the preceding 2 weeks: fasting/pre-prandial = 5.3, post prandial 1 hour of = 7.8 or post prandial 2 hours of = 6.7 mmol/L
6. Not on any hypoglycaemic drug treatment

Exclusion criteria:
1. Any contraindication to metformin
2. History of prepregnant hyperglycaemia
2.1. Type 2 diabetes,
2.2. Impaired glucose tolerance
2.3. Fasting glycaemia
3. Diagnostic 75g OGTT: fasting plasma glucose = 7 or 2-hour glucose = 11.1 mmol/L


Age minimum:
Age maximum:
Gender: Female

Health Condition(s) or Problem(s) studied

Mild gestational diabetes mellitus
Nutritional, Metabolic, Endocrine
Mild gestational diabetes mellitus

Intervention(s)

Participants who are diagnosed as gestational diabetes and fulfilled the inclusion and exclusion criteria will be recruited. Blood samples for HbA1c are obtained and analysed by centre’s laboratory.

Participants are then randomised to either the metformin at a dose of 500 mg (1 tablet) twice daily or identical looking placebo tablet twice daily taken by mouth after breakfast and dinner. Trial interventions continue to delivery.

Randomisation sequence is generated using a random number generator by a co-investigator who is not involved in recruitment, numbered and with strict sequential allocation by recruitment order. Participants and investigators are blinded.

Both arms receive the same advice on diet and lifestyle modification. Participants are followed up in antenatal clinic at least biweekly and monitored with weekly 4 points blood sugar profile consisting of fasting pre breakfast and 2-hour post meals. Open label metformin to a maximum dose of 1500 mg daily in divided doses can be added if needed based on above target BSP readings with treatment threshold according to local practice. The open label metformin are from a different manufacturer and visually distinct from trial metformin/placebo tablets.

Standard institutional care for gestational diabetes applies to both arms. Blood is drawn at 36 weeks or as soon as possible thereafter to determine HbA1c level. Outcomes will be collected from participants’ hospital and laboratory records.

Primary Outcome(s)

HbA1c is measured using blood samples at baseline and 36 weeks

Secondary Outcome(s)

1. Tolerability is measured using a symptom questionnaire at four weeks after recruitment and at 36 weeks gestation
2. Open label metformin use in pregnancy is measured by checking participants’ hospital records after delivery
3. Insulin use in pregnancy is measured by checking participants’ hospital records after delivery
4. Pregnancy induced hypertension is defined as blood pressure more than 140/90mmHg on 2 occasions with 4 hours apart after 20 weeks of gestation and established by checking participants’ hospital records after delivery
5. Gestational age at delivery (preterm labour < 37 weeks)
6. Intervention to delivery interval is measured by checking participants’ hospital records after delivery
7. Induction of labour is measured by checking participants’ hospital records after delivery
8. Epidural analgesia in labour is measured by checking participants’ hospital records after delivery
9. Mode of delivery
9.1. Indication for Caesarean delivery
10. Blood loss at delivery is measured as:
10.1. Postpartum haemorrhage = 500 ml
10.2. Major postpartum haemorrhage = 1000 ml
11. Third or fourth degree perineal tear as reported at birth
12. Reported shoulder dystocia
13. Birth weight is measured by checking participants’ hospital records after delivery
14. Placenta weight is measured by checking participants’ hospital records after delivery
15. Umbilical cord arterial pH at birth
16. Neonatal birth injury
17. Neonatal jaundice
18. Neonatal admission and indication

Secondary ID(s)

2017813-5489

Source(s) of Monetary Support

Obstetric and Gynaecology Department, University Malaya Medical Centre

Ethics review

Status:
Approval date:
Contact:

University Malaya Medical Centre, 11/10/2017, ref: 2017813-5489

Results

• Results available: Yes
• Date Completed: 31/01/2019