. 2018 Jun 15;7:212523. doi: 10.7573/dic.212523

Table 2.

Randomized controlled trials comparing metformin with insulin or glyburide in women with gestational diabetes.

Author, country, year published	Trial design	Key outcomes
Moore et al., USA, 2007 [27]	63 women with GDM; Metformin versus insulin	No difference in maternal or fetal outcomes. No patient on metformin required insulin. Trial was underpowered.
Rowan et al., Australia & New Zealand, 2008 [22]	751 women with GDM at 20–33 weeks of gestation; metformin versus insulin	46.3% metformin users required supplemental insulin. No difference in primary composite outcome (composite of neonatal hypoglycemia, respiratory distress, need for phototherapy, birth trauma, 5-minute Apgar score <7 or prematurity) – RR 0.99, 95% CI: 0.80–1.23. No difference in secondary outcomes (neonatal anthropometry, maternal glycemic control, PIH and postpartum glucose tolerance). Better patient acceptability.
Silva et al., Brazil, 2010 [28]	72 women with GDM; metformin (n=40) versus glyburide (n=32)	Less maternal weight gain with metformin (7.6 versus 10.3 kg, p=0.02). Similar fasting and postprandial glucose, birth weight, LGA and neonatal hypoglycemia. Similar rates of treatment failure with need for insulin.
Moore et al., USA, 2010 [29]	149 GDM women; metformin (n=75) versus glyburide (n=74)	34.7% in metformin group and 16.2% in glyburide group required insulin. Higher failure rate of metformin.
Ijas et al., Finland, 2011 [30]	100 GDM women; metformin versus insulin	No differences in LGA, birth weight, mean cord artery pH or neonatal morbidity. Higher rates of Caesarian section with metformin (RR 1.9, 95% CI: 0.99–3.71). 32% women in metformin group required supplemental insulin. When compared to those who did not need insulin, these women had the following: Higher BMI (36 versus 30 kg/m², p=0.002). Higher fasting glucose (6.1 versus 5.0 mmol/l, p=0.001). Earlier need for medical treatment for GDM (26 versus 31 weeks of gestation, p=0.002).
Niromanesh et al., Iran, 2012 [31]	160 women with GDM between 20 and 34 weeks; metformin versus insulin	Similar fasting and postprandial glucose. No difference in neonatal and obstetric complications. 14% required supplemental insulin. Less maternal weight gain with metformin (p<0.001). Less risk of birth weight > 90th centile (RR 0.5, 95% CI: 0.3–0.9, p=0.012) with metformin.
Silva et al., Brazil, 2012 [32]	200 GDM women; metformin [104] versus glyburide [96]	Lower maternal weight gain with metformin (7.78 versus 9.84, p=0.04). Lower birth weight (3193 versus 3387 kg, p=0.01) and ponderal index (2.87 versus 2.96, p=0.05) with metformin. Greater neonatal hypoglycemia with glyburide. No difference in Caesarian sections, gestational age at delivery, LGA, neonatal hypoglycemia, NICU admissions or perinatal death.
Mesdaghinia et al., Iran, 2013 [33]	200 GDM women at 24–34 weeks; metformin versus insulin	22% in metformin group required supplemental insulin. No difference in glycemic control, PIH, route of delivery. No difference in birth weight, dystocia, Apgar score, hypoglycemia and still birth. Higher maternal weight gain, preterm labor and end of pregnancy HbA1c in insulin group. Higher incidence of neonatal jaundice, respiratory distress and NICU admission in insulin group.
Spaulonci et al., Brazil, 2013 [34]	94 women with GDM; metformin versus insulin	Less maternal weight gain (p=0.02) and lower frequency of neonatal hypoglycemia (p=0.032) with metformin. 26% metformin users required supplemental insulin. Predictors of need for insulin were early gestational age at GDM diagnosis and higher mean pre-treatment glucose.
Tertti et al., Finland, 2013 [35]	217 GDM patients; metformin versus insulin	No difference in birth weight, neonatal or maternal outcomes. 20.9% required supplemental insulin. Factors predicting need for insulin – older age (p=0.04), earlier gestational age at diagnosis (p=0.01) and higher baseline serum fructosamine concentration.
Ruholamin et al., Iran, 2014 [36]	109 GDM women; metformin versus insulin	Similar glycemic control and other maternal outcomes, including preterm delivery. No difference in neonatal outcomes (hypoglycemia, birth weight, Apgar score, hyperbilirubinemia).
George et al., India, 2015 [37]	159 South Indian women with GDM; metformin versus glyburide	Primary outcome (composite of macrosomia, hypoglycemia, need for phototherapy, respiratory distress, stillbirth or neonatal death and birth trauma): 35% in glyburide group and 18.9% in metformin group. Higher rate of neonatal hypoglycemia with glyburide (12.5%) versus none with metformin. No difference in birth weight, glycemic control, PIH, preterm birth, mode of delivery or complications of delivery.
Ainuddin et al., Pakistan, 2015 [38]	150 women with GDM; metformin versus insulin	42.7% in metformin group required supplemental insulin. Less maternal weight gain with metformin (9.8±1.5 kg) than insulin (12.5±1.1 kg). Less risk of preeclampsia with metformin. Lower mean birth weight (3.4±0.4 versus 3.7±0.5 kg, p<0.01) and less neonatal morbidity with metformin.
Ashoush et al., Egypt, 2016 [39]	Women with GDM at 26–32 weeks. Metformin (n=47) versus insulin (n=48)	23.4% metformin users needed supplemental insulin. Metformin associated with less maternal weight gain (p<0.001) and lower fasting glucose during first and last 2 weeks of treatment (p=0.014 and 0.008, respectively). Fetal and maternal outcomes similar.
Nachum et al., Israel, 2017 [40]	53 patients on glyburide and 51 patients on metformin	Similar glycemic control. Failure rate 34% with glyburide, 29% with metformin. Obstetric and neonatal outcomes comparable.
Arshad et al., Pakistan, 2017 [41]	71 GDM women; metformin versus insulin	Metformin associated with lower birth weight. Higher HbA1c at term and more Caesarian sections with insulin. More babies born after 38 weeks with insulin.

GDM, gestational diabetes; HbA1c, hemoglobin A1c; LGA, large for gestational age; NICU, neonatal intensive care unit; pH, potential hydrogen; PIH, pregnancy-induced hypertension; RR, relative risk.