Original Article Comparison of neonatal outcomes in women with gestational diabetes with moderate hyperglycaemia on metformin or glibenclamide – A randomised controlled trial Anne GEORGE, 1 Jiji E. MATHEWS, 1 Dibu SAM, 1 Manisha BECK, 1 Santosh J. BENJAMIN, 1 Anuja ABRAHAM, 1 Balevendra ANTONISAMY, 2 Atanu K. JANA 3 and Nihal THOMAS 4 1 Department of Obstetrics and Gynaecology, Christian Medical College, 2 Department of Biostatistics, Christian Medical College, 3 Department of Neonatology, Christian Medical College, and 4 Department of Endocrinology, Christian Medical College, Vellore, India Background: Two oral hypoglycaemic agents, metformin and glibenclamide, have been compared with insulin in separate large randomised controlled trials and have been found to be as effective as insulin in gestational diabetes. However, very few trials have compared metformin with glibenclamide. Materials and Methods: Of 159 South Indian women with fasting glucose ≥5.5 mmol/l and ≤7.2 mmol/l and/or 2-h post-prandial value ≥6.7 mmol/l and ≤13.9 mmol/l after medical nutritional therapy consented to be randomised to receive either glibenclamide or metformin. 80 women received glibenclamide and 79 received metformin. Neonatal outcomes were assessed by neonatologists who were unaware that the mother was part of a study and were recorded by assessors blinded to the medication the mother was given. The primary outcome was a composite of neonatal outcomes namely macrosomia, hypoglycaemia, need for phototherapy, respiratory distress, stillbirth or neonatal death and birth trauma. Secondary outcomes were birthweight, maternal glycaemic control, pregnancy induced hypertension, preterm birth, need for induction of labour, mode of delivery and complications of delivery. Results: Baseline characteristics were similar but for the higher fasting triglyceride levels in women on metformin. The primary outcome was seen in 35% of the glibenclamide group and 18.9% of the metformin group [95% CI 16.1 (2.5, 29.7); P = 0.02]. The difference in outcome related to a higher rate of neonatal hypoglycaemia in the glibenclamide group (12.5%) versus none in the metformin group [95% CI 12.5(5.3, 19.7); P = 0.001]. Secondary outcomes in both groups were similar. Conclusion: In a south Indian population with gestational diabetes, metformin was associated with better neonatal outcomes than glibenclamide. Key words: gestational diabetes, glibenclamide, metformin, neonatal hyperbilirubinemia, neonatal hypoglycaemia. Background Over the last decade, a number of large studies 1–5 have made a major impact on the management of gestational diabetes mellitus (GDM). Two large randomised controlled studies 2,3 have now established that the treatment of mild gestational diabetes can prevent adverse perinatal outcomes. There has been a steep increase in the prevalence of gestational diabetes worldwide 6,7 in the last decade. Until recently, the only mode of treatment for gestational diabetes mellitus not controlled with medical nutritional therapy (MNT) was insulin. Besides having to be administered parenterally, insulin administration has the disadvantage of being expensive, dependent on glucose monitoring, requiring refrigeration and significant training for acquiring the technique for administration. 8,9 Two oral hypoglycaemic agents, metformin and glibenclamide, have been compared with insulin in separate randomised controlled trials 4,5 and have been found to be as effective as insulin. Glibenclamide is a sulfonylurea that achieves glycaemic control by stimulating insulin secretion. It is known to cause hypoglycaemia and weight gain in the mother. According to earlier studies, 10 glibenclamide did not cross the placental barrier. Recent studies have revealed that umbilical cord plasma glibenclamide levels averaged 70% of maternal concentrations. 11 This should be considered especially if glibenclamide doses are increased to achieve stricter glycaemic control. Metformin, a biguanide derivative, works primarily by reducing hepatic glucose output, improving peripheral glucose uptake, reducing endogenous insulin levels and reducing insulin resistance probably by Correspondence: Dr Jiji E. Mathews, Department of Obstetrics & Gynaecology, Christian Medical College and Hospital, Vellore – 632 004, Tamilnadu, India. Email: coronistrial@yahoo.co.in Received 17 June 2014; accepted 14 September 2014. © 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists 47 Australian and New Zealand Journal of Obstetrics and Gynaecology 2015; 55: 47–52 DOI: 10.1111/ajo.12276 he Australian and New Zealand Journal of Obstetrics and Gynaecology