Glyburide and Metformin for the Treatment of Gestational Diabetes Mellitus. Systematic Review

Completed

• Conditions: Gestational Diabetes Mellitus
• Interventions: Drug: Metformin vs Glyburide trials; Drug: Glyburide vs Insulin trials; Drug: Metformin vs Insulin trials

• Registration Number: NCT01998113
• Lead Sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

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.

Results of the systematic review will be published following PRISMA guidance.

Study Timeline

• Study Start: 2013-03
• Status Verified: 2013-11
• Study First Submitted: 2013-11-08
• Study First Submitted QC: 2013-11-25
• Study First Posted: 2013-11-28
• Primary Completion: 2014-05
• Study Completion: 2014-05
• Last Update Submitted: 2015-03-23
• Last Update Posted: 2015-03-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 2509

Inclusion Criteria

• RCT
• GDM
• 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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Metformin (Metformin vs Glyburide)	Metformin vs Glyburide trials	Metformin vs Glyburide trials
Insulin (Glyburide vs Insulin)	Glyburide vs Insulin trials	Glyburide vs Insulin trials
Glyburide (Metformin vs Glyburide)	Metformin vs Glyburide trials	Metformin vs Glyburide trials
Glyburide (Glyburide vs Insulin)	Glyburide vs Insulin trials	Glyburide vs Insulin trials
Metformin (Metformin vs Insulin)	Metformin vs Insulin trials	Metformin vs Insulin trials
Insulin (Metformin vs Insulin)	Metformin vs Insulin trials	Metformin vs Insulin trials

Primary Outcome Measures

Name	Time	Method
total maternal weight gain	during pregnancy	mean difference of total maternal weight gain (as defined by the authors)
severe maternal hypoglycemia	from enrollment to delivery	relative risk of severe maternal hypoglycemia (as defined by the authors)
preeclampsia	during pregnancy or puerperium	relative risk of preeclampsia (as defined by the authors)
cesarean section	at the end of pregnancy	relative risk of cesarean section (as defined by the authors)
gestational age at birth	at birth	mean difference of gestational age at birth (as defined by the authors)
preterm birth	at birth	relative risk of preterm birth (as defined by the authors)
birthweight	at birth	mean difference of birthweight (as defined by the authors)
macrosomia	at birth	relative risk of macrosomia (defined as birthweight \>=4000 g)
large-for-gestational age newborn	at birth	relative risk of large-for-gestational age newborn (as defined by the authors)
small-for-gestational age newborn	at birth	relative risk of small-for-gestational age newborn (as defined by the authors)
neonatal hypoglycemia	in the neonatal period	relative risk of neonatal hypoglycemia (as provided by the authors)
perinatal mortality	in the perinatal period	relative risk of perinatal mortality (as defined by the authors)
insulin treatment	from enrollment to delivery	relative risk of insulin treatment (for trials comparing metformin vs glyburide)
3rd trimester glycated hemoglobin	3rd trimester of pregnancy	mean difference of 3rd trimester glycated hemoglobin

Secondary Outcome Measures

Name	Time	Method
maternal weight gain since enrollment	in the period from enrollment to delivery	mean difference of maternal weight gain since enrollment (as defined by the authors)
pregnancy-induced hypertension	during pregnancy	relative risk of pregnancy-induced hypertension (as defined by the authors)
induction of labour	at the end of pregnancy	relative risk of induction of labour (as described by the authors)
cord C peptide	at birth	mean difference of cord C peptide (as defined by the authors)
cord insulin	at birth	mean difference of cord insulin (as defined by the authors)
abnormal 1 min Apgar	at birth	relative risk of abnormal 1 min Apgar (defined as lower than 7)
abnormal 5 min Apgar	at birth	relative risk of abnormal 5 min Apgar (defined as lower than 7)
obstetric trauma	at birth	relative risk of obstetric trauma (as defined by the authors)
severe neonatal hypoglycemia	in the neonatal period	relative risk of severe neonatal hypoglycemia (as defined by the authors)
neonatal jaundice	in the neonatal period	relative risk of neonatal jaundice (as defined by the authors)
significant respiratory distress	in the neonatal period	relative risk of significant respiratory distress (described as respiratory distress syndrome or requiring respiratory support)
stillbirth	in the antenatal period	relative risk of stillbirth (as defined by the authors)
neonatal mortality	in the neonatal period	relative risk of neonatal mortality (as defined by the authors)
Neonatal Intensive Care Unit (NICU) admittance	in the neonatal period	relative risk of NICU admittance (as defined by the authors)
fasting blood glucose	in the period from enrollment to delivery	mean difference of fasting blood glucose (as defined by the authors)
postprandial blood glucose	in the period from enrollment to delivery	mean difference of postprandial blood glucose (as defined by the authors)

Trial Locations

Locations (1)

Hospital de la Santa Creu i Sant Pau; 🇪🇸 Barcelona, Spain