Comparative efficacy and safety of OADs in management of GDM: network meta-analysis of randomized controlled trials

J Clin Endocrinol Metab. 2015 May;100(5):2071-80. doi: 10.1210/jc.2014-4403. Epub 2015 Mar 24.


Objective: We conducted a network meta-analysis to evaluate the efficacy and safety of oral antidiabetic drugs (OADs) for gestational diabetes.

Data sources: We searched PubMed, the Cochrane Library,, and related reviews from inception to October 2014.

Study selection: We included randomized clinical trials comparing efficacy and safety between different OADs or OADs vs insulin in patients with gestational diabetes.

Data synthesis: We included 18 randomized clinical trials. Traditional and network meta-analyses were performed to compare different OADs or OADs vs insulin. Traditional meta-analyses confirmed that there was no significant difference in maternal fasting blood glucose or glycated hemoglobin levels in patients treated with insulin, metformin, and glyburide. Compared to insulin, metformin was associated with lower maternal weight gain (weighted mean difference [WMD], -1.49 kg; 95% confidence interval [CI], -2.26 to -0.31), shorter gestational age (WMD, -0.16 wk; 95% CI, -0.30 to -0.03), and increased incidence of premature birth (odds ratio [OR], 1.63; 95% CI, 1.07 to 2.48). Compared to insulin, glyburide was associated with higher neonatal birth weight (WMD, 130.68 g; 95% CI, 55.98 to 205.38), increased incidence of neonatal hypoglycemia (OR, 2.64; 95% CI, 1.59 to 4.38), and increased incidence of macrosomia (OR, 3.09; 95% CI, 1.59 to 6.04). Network meta-analysis revealed that glyburide was associated with higher maternal weight gain, higher neonatal birth weight, increased incidence of neonatal hypoglycemia, and increased incidence of macrosomia than was metformin.

Conclusion: Both metformin and glyburide are suitable for use in the management of gestational diabetes because of good glycemic control. However, glyburide treatment is associated with increased risk of neonatal hypoglycemia, high maternal weight gain, high neonatal birth weight, and macrosomia.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Blood Glucose
  • Diabetes, Gestational / blood
  • Diabetes, Gestational / drug therapy*
  • Female
  • Glyburide / administration & dosage
  • Glyburide / adverse effects
  • Glyburide / therapeutic use
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects*
  • Hypoglycemic Agents / therapeutic use
  • Insulin / administration & dosage
  • Insulin / adverse effects
  • Insulin / therapeutic use
  • Metformin / administration & dosage
  • Metformin / adverse effects
  • Metformin / therapeutic use
  • Pregnancy
  • Pregnancy Outcome
  • Randomized Controlled Trials as Topic
  • Treatment Outcome


  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Metformin
  • Glyburide