Glyburide and Metformin for the Treatment of Gestational Diabetes Mellitus. A Systematic Review and Meta-analysis of Randomized Controlled Trials Comparing These Drugs Either vs Insulin or vs Each Other.
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 2,509
- Locations
- 1
- Primary Endpoint
- 3rd trimester glycated hemoglobin
Study Overview
Brief Summary
Since the publication in the New England Journal of Medicine (NEJM) in 2000 of the Langer's trial comparing glyburide vs insulin in the treatment of gestational diabetes mellitus (GDM), additional studies of oral agents for the treatment of GDM have been published (observational, randomized controlled trials (RCT), and trials using other drugs like metformin).
Some meta-analysis to summarize the evidence have been published: Nicholson 2009 (including 4 RCT addressing different drugs), Dhulkotia 2010 (including 6 RCT addressing different drugs, the meta-analysis combining all drugs altogether), Gui 2013 (including 5 RCT addressing metformin vs insulin).
Oral agents are increasingly used for the treatment of GDM. Investigators aim to update the evidence on RCTs comparing glyburide and metformin vs insulin or between them and summarize this evidence using meta-analysis tools. Specifically, investigators aim at producing distinct meta-analyses for each one of the three drug comparisons. This information is not available in the literature since the most recent systematic reviews specifically dealing on oral agents for the treatment of GDM have addressed a single drug comparison (Gui 2013) or have combined different drug comparisons into a single meta-analysis (Dhulkotia 2010)
Detailed Description
This project involves the systematic review of RCT addressing the use of glyburide or metformin for the treatment of GDM. The review will include RCT comparing these drugs versus insulin or making direct comparisons between the two oral agents in pregnant women with GDM.
Investigators have pre-specified a series of maternal and fetal outcomes of interest.
A comprehensive electronic search strategy will be complemented with a search of bibliographies from relevant studies and the contact of authors from the eligible studies regarding issues on study design or information on primary outcomes.
The risk of bias of included studies will be analyzed and this information used to perform sensitivity analyses. If possible, data from original studies will be pooled into relative risks for dichotomous outcomes and mean differences for continuous outcomes.
Heterogeneity will be explored for all the analyses. Analyses will be undertaken using a fixed effects model that will be repeated using a random effects model in case of substantial heterogeneity.
Study Design
- Study Type
- Observational
- Time Perspective
- Retrospective
Eligibility Criteria
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •comparing Glyburide vs Insulin, Metformin vs Insulin or Metformin vs Glyburide
- •data on fetal and/or maternal outcomes
- •full text available
Exclusion Criteria
- •significant overlap with other articles of the same group
Arms & Interventions
Insulin (Glyburide vs Insulin)
Glyburide vs Insulin trials
Intervention: Glyburide vs Insulin trials (Drug)
Metformin (Metformin vs Insulin)
Metformin vs Insulin trials
Intervention: Metformin vs Insulin trials (Drug)
Glyburide (Glyburide vs Insulin)
Glyburide vs Insulin trials
Intervention: Glyburide vs Insulin trials (Drug)
Insulin (Metformin vs Insulin)
Metformin vs Insulin trials
Intervention: Metformin vs Insulin trials (Drug)
Metformin (Metformin vs Glyburide)
Metformin vs Glyburide trials
Intervention: Metformin vs Glyburide trials (Drug)
Glyburide (Metformin vs Glyburide)
Metformin vs Glyburide trials
Intervention: Metformin vs Glyburide trials (Drug)
Outcomes
Primary Outcomes
3rd trimester glycated hemoglobin
Time Frame: 3rd trimester of pregnancy
mean difference of 3rd trimester glycated hemoglobin
total maternal weight gain
Time Frame: during pregnancy
mean difference of total maternal weight gain (as defined by the authors)
severe maternal hypoglycemia
Time Frame: from enrollment to delivery
relative risk of severe maternal hypoglycemia (as defined by the authors)
preeclampsia
Time Frame: during pregnancy or puerperium
relative risk of preeclampsia (as defined by the authors)
cesarean section
Time Frame: at the end of pregnancy
relative risk of cesarean section (as defined by the authors)
gestational age at birth
Time Frame: at birth
mean difference of gestational age at birth (as defined by the authors)
preterm birth
Time Frame: at birth
relative risk of preterm birth (as defined by the authors)
birthweight
Time Frame: at birth
mean difference of birthweight (as defined by the authors)
macrosomia
Time Frame: at birth
relative risk of macrosomia (defined as birthweight \>=4000 g)
large-for-gestational age newborn
Time Frame: at birth
relative risk of large-for-gestational age newborn (as defined by the authors)
small-for-gestational age newborn
Time Frame: at birth
relative risk of small-for-gestational age newborn (as defined by the authors)
neonatal hypoglycemia
Time Frame: in the neonatal period
relative risk of neonatal hypoglycemia (as provided by the authors)
perinatal mortality
Time Frame: in the perinatal period
relative risk of perinatal mortality (as defined by the authors)
insulin treatment
Time Frame: from enrollment to delivery
relative risk of insulin treatment (for trials comparing metformin vs glyburide)
Secondary Outcomes
- maternal weight gain since enrollment(in the period from enrollment to delivery)
- pregnancy-induced hypertension(during pregnancy)
- induction of labour(at the end of pregnancy)
- cord C peptide(at birth)
- cord insulin(at birth)
- abnormal 1 min Apgar(at birth)
- abnormal 5 min Apgar(at birth)
- obstetric trauma(at birth)
- severe neonatal hypoglycemia(in the neonatal period)
- neonatal jaundice(in the neonatal period)
- significant respiratory distress(in the neonatal period)
- stillbirth(in the antenatal period)
- neonatal mortality(in the neonatal period)
- Neonatal Intensive Care Unit (NICU) admittance(in the neonatal period)
- fasting blood glucose(in the period from enrollment to delivery)
- postprandial blood glucose(in the period from enrollment to delivery)