Comparative Efficacy and Safety of Oral Antidiabetic Drugs and Insulin in Treating Gestational Diabetes Mellitus: An Updated PRISMA-compliant Network Meta-Analysis

Medicine (Baltimore). 2017 Sep;96(38):e7939. doi: 10.1097/MD.0000000000007939.


Background: The safety and efficacy of different drugs in treatment of gestational diabetes mellitus (GDM) patients who could not maintain normal glucose level only through diet and exercise remains to be debated. We performed this network meta-analysis (NAM) to compare and rank different antidiabetic drugs in glucose level control and pregnancy outcomes in GDM patients.

Methods: We searched PubMed, Cochrane Library, Web of Science, and Embase up to December 31, 2016. Randomized controlled trials (RCTs) related to different drugs in the treatment of GDM patients were enrolled. We extracted the relevant information and assessed the risk of bias with the Cochrane risk of bias tool. We did pair-wise meta-analyses using the fixed-effects model or random-effects model and then adopted random-effects NAM combining both direct and indirect evidence within a Bayesian framework, to calculate the odds ratio (OR) or standardized mean difference (SMD) and to draw a surface under the cumulative ranking curve of the neonatal and maternal outcomes of different treatments in GDM patients.

Results: Thirty-two randomized controlled trials (RCTs) were included in this NAM, including 6 kinds of treatments (metformin, metformin plus insulin, insulin, glyburide, acarbose, and placebo). The results of the NAM showed that regarding the incidence of macrosomia and LGA, metformin had lower incidence than glyburide (OR, 0.5411 and 0.4177). In terms of the incidence of admission to the NICU, insulin had higher incidence compared with glyburide (OR, 1.844). As for the incidence of neonatal hypoglycemia, metformin had lower incidence than insulin and glyburide (OR, 0.6331 and 0.3898), and insulin was lower than glyburide (OR, 0.6236). For mean birth weight, metformin plus insulin was lower than insulin (SMD, -0.5806), glyburide (SMD, -0.7388), and placebo (SMD, -0.6649). Besides, metformin was observed to have lower birth weight than glyburide (SMD, 0.2591). As for weight gain, metformin and metformin plus insulin were lower than insulin (SMD, -0.9166, -1.53). Ranking results showed that glyburide might be the optimum treatment regarding average glucose control, and metformin is the fastest in glucose control for GDM patients; glyburide have the highest incidence of macrosomia, preeclampsia, hyperbilirubinemia, neonatal hypoglycemia, shortest gestational age at delivery, and lowest mean birth weight; metformin (plus insulin when required) have the lowest incidence of macrosomia, PIH, LGA, RDS, low gestational age at delivery, and low birth weight. Besides, insulin had the highest incidence of NICU admission, acarbose had the lowest risk of neonatal hypoglycemia.

Conclusion: Our study concluded that metformin is fastest in glucose control, with a more favorable pregnancy outcomes-would be a better option, but its rate of glucose control is the lowest.However, glyburide is the optimumtreatment regarding the rate of glucose control, but withmore adverse outcomes. This NAMbased on 32 RCTs will strongly help to guide further development of management for GDM patients, clinicians should carefully balance the risk-benefit profile of different treatments according to various situations.

Publication types

  • Meta-Analysis

MeSH terms

  • Administration, Oral
  • Adult
  • Blood Glucose / drug effects
  • Comparative Effectiveness Research
  • Diabetes, Gestational / blood
  • Diabetes, Gestational / drug therapy*
  • Female
  • Fetal Macrosomia / chemically induced
  • Fetal Macrosomia / epidemiology
  • Glyburide / administration & dosage*
  • Glyburide / adverse effects
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Incidence
  • Infant, Newborn
  • Insulin / administration & dosage*
  • Insulin / adverse effects
  • Metformin / administration & dosage*
  • Metformin / adverse effects
  • Pregnancy
  • Randomized Controlled Trials as Topic


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