A meta-analysis of 13 randomized controlled trials involving a total of 2 151 patients assessed the efficacy and safety of oral antidiabetic drugs (metformin and glyburide). A significant increase in the risk for preterm births (65 vs 44 events, RR, 1.51; 95% CI, 1.04-2.19, p = 0.03; n=1102) was found with metformin compared to insulin. However, a significant decrease in the risk for gestational hypertension (RR, 0.54; 95% CI, 0.31-0.91, p = 0.02) was found. Postprandial glucose levels also decreased significantly in patients receiving metformin (MD, -2.47 mg/dL; 95% CI, -4.00, -0.94, p = 0.002). There was no significant difference between the two groups for the remaining outcomes (macrosomia, large for gestational age, shoulder dystocia, neonatal hypoglycemia, neonatal mortality, caesarean section, pre-eclampsia, or induction of labour).
An open RCT including 751 women with gestational diabetes mellitus (defined as a fasting capillary blood glucose above 5.4 mmol/l or more than one 2-hour postprandial blood glucose above 6.7 mmol/l) at 20 to 33 weeks of gestation compared metformin (with supplemental insulin if required to reach a fasting glucose level <5.5 mmol/l or a postprandial level <7.0 mmol/l) with insulin. Of the women assigned to metformin, 92.6% continued to receive metformin, and 46.3% received supplemental insulin. The rate of the primary composite outcome (neonatal hypoglycemia, respiratory distress, need for phototherapy, birth trauma, 5-minute Apgar score less than 7, or prematurity) was 32.0% in the group assigned to metformin and 32.2% in the insulin group. (RR 1.00, 95% CI 0.90 to 1.10).More women in the metformin group stated that they would choose their allocated therapy (76.6% vs. 27.2%).
Comment: The quality of evidence is downgraded by imprecise results (few events for individual end points).