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

Gestational Diabetes Mellitus Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01998113
• Other study ID #: IIBSP-ADO-2013-153
• Status: Completed
• Phase: N/A
• First received: November 8, 2013
• Last updated: March 23, 2015
• Start date: March 2013
• Est. completion date: May 2014

Study information

• Verified date: November 2013
• Source: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ethics Committee
• Study type: Observational

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2509
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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

Time Perspective: Retrospective

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes, Gestational
• Gestational Diabetes Mellitus

Intervention

Drug:
• Glyburide vs Insulin trials
Affecting groups 1 and 2
• Metformin vs Insulin trials
Affecting groups 3 and 4
• Metformin vs Glyburide trials
Affecting groups 5 and 6

Locations

Country	Name	City	State
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Country where clinical trial is conducted

Spain, 

References & Publications (6)

Dhulkotia JS, Ola B, Fraser R, Farrell T. Oral hypoglycemic agents vs insulin in management of gestational diabetes: a systematic review and metaanalysis. Am J Obstet Gynecol. 2010 Nov;203(5):457.e1-9. doi: 10.1016/j.ajog.2010.06.044. Epub 2010 Aug 24. Review. — View Citation

Gui J, Liu Q, Feng L. Metformin vs insulin in the management of gestational diabetes: a meta-analysis. PLoS One. 2013 May 27;8(5):e64585. doi: 10.1371/journal.pone.0064585. Print 2013. — View Citation

Langer O, Conway DL, Berkus MD, Xenakis EM, Gonzales O. A comparison of glyburide and insulin in women with gestational diabetes mellitus. N Engl J Med. 2000 Oct 19;343(16):1134-8. — View Citation

Nicholson W, Bolen S, Witkop CT, Neale D, Wilson L, Bass E. Benefits and risks of oral diabetes agents compared with insulin in women with gestational diabetes: a systematic review. Obstet Gynecol. 2009 Jan;113(1):193-205. doi: 10.1097/AOG.0b013e318190a459. Review. — View Citation

Rowan JA, Hague WM, Gao W, Battin MR, Moore MP; MiG Trial Investigators. Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med. 2008 May 8;358(19):2003-15. doi: 10.1056/NEJMoa0707193. Erratum in: N Engl J Med. 2008 Jul 3;359(1):106. — View Citation

Silva JC, Fachin DR, Coral ML, Bertini AM. Perinatal impact of the use of metformin and glyburide for the treatment of gestational diabetes mellitus. J Perinat Med. 2012 Jan 10;40(3):225-8. doi: 10.1515/jpm-2011-0175. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	3rd trimester glycated hemoglobin	mean difference of 3rd trimester glycated hemoglobin	3rd trimester of pregnancy	No
Primary	total maternal weight gain	mean difference of total maternal weight gain (as defined by the authors)	during pregnancy	No
Primary	severe maternal hypoglycemia	relative risk of severe maternal hypoglycemia (as defined by the authors)	from enrollment to delivery	No
Primary	preeclampsia	relative risk of preeclampsia (as defined by the authors)	during pregnancy or puerperium	No
Primary	cesarean section	relative risk of cesarean section (as defined by the authors)	at the end of pregnancy	No
Primary	gestational age at birth	mean difference of gestational age at birth (as defined by the authors)	at birth	No
Primary	preterm birth	relative risk of preterm birth (as defined by the authors)	at birth	No
Primary	birthweight	mean difference of birthweight (as defined by the authors)	at birth	No
Primary	macrosomia	relative risk of macrosomia (defined as birthweight >=4000 g)	at birth	No
Primary	large-for-gestational age newborn	relative risk of large-for-gestational age newborn (as defined by the authors)	at birth	No
Primary	small-for-gestational age newborn	relative risk of small-for-gestational age newborn (as defined by the authors)	at birth	No
Primary	neonatal hypoglycemia	relative risk of neonatal hypoglycemia (as provided by the authors)	in the neonatal period	No
Primary	perinatal mortality	relative risk of perinatal mortality (as defined by the authors)	in the perinatal period	No
Primary	insulin treatment	relative risk of insulin treatment (for trials comparing metformin vs glyburide)	from enrollment to delivery	No
Secondary	fasting blood glucose	mean difference of fasting blood glucose (as defined by the authors)	in the period from enrollment to delivery	No
Secondary	postprandial blood glucose	mean difference of postprandial blood glucose (as defined by the authors)	in the period from enrollment to delivery	No
Secondary	maternal weight gain since enrollment	mean difference of maternal weight gain since enrollment (as defined by the authors)	in the period from enrollment to delivery	No
Secondary	pregnancy-induced hypertension	relative risk of pregnancy-induced hypertension (as defined by the authors)	during pregnancy	No
Secondary	induction of labour	relative risk of induction of labour (as described by the authors)	at the end of pregnancy	No
Secondary	cord C peptide	mean difference of cord C peptide (as defined by the authors)	at birth	No
Secondary	cord insulin	mean difference of cord insulin (as defined by the authors)	at birth	No
Secondary	abnormal 1 min Apgar	relative risk of abnormal 1 min Apgar (defined as lower than 7)	at birth	No
Secondary	abnormal 5 min Apgar	relative risk of abnormal 5 min Apgar (defined as lower than 7)	at birth	No
Secondary	obstetric trauma	relative risk of obstetric trauma (as defined by the authors)	at birth	No
Secondary	severe neonatal hypoglycemia	relative risk of severe neonatal hypoglycemia (as defined by the authors)	in the neonatal period	No
Secondary	neonatal jaundice	relative risk of neonatal jaundice (as defined by the authors)	in the neonatal period	No
Secondary	significant respiratory distress	relative risk of significant respiratory distress (described as respiratory distress syndrome or requiring respiratory support)	in the neonatal period	No
Secondary	stillbirth	relative risk of stillbirth (as defined by the authors)	in the antenatal period	No
Secondary	neonatal mortality	relative risk of neonatal mortality (as defined by the authors)	in the neonatal period	No
Secondary	Neonatal Intensive Care Unit (NICU) admittance	relative risk of NICU admittance (as defined by the authors)	in the neonatal period	No