Clinical trial NCT01998113: Glyburide and Metformin for the Treatment of Gestational Diabetes Mellitus. Systematic Review
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.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Gestational Diabetes Mellitus
Keywords: gestational diabetes mellitus
glyburide
metformin
oral agents
insulin
outcomes
Lead sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Sponsor class: OTHER
First posted: 2013-11-28
Enrollment: 2509
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: pregnant women with gestational diabetes mellitus requiring drug treatment

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.

Eligibility criteria: 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

Primary outcomes:
measure: 3rd trimester glycated hemoglobin
timeFrame: 3rd trimester of pregnancy
measure: total maternal weight gain
timeFrame: during pregnancy
measure: severe maternal hypoglycemia
timeFrame: from enrollment to delivery
measure: preeclampsia
timeFrame: during pregnancy or puerperium
measure: cesarean section
timeFrame: at the end of pregnancy
measure: gestational age at birth
timeFrame: at birth
measure: preterm birth
timeFrame: at birth
measure: birthweight
timeFrame: at birth
measure: macrosomia
timeFrame: at birth
measure: large-for-gestational age newborn
timeFrame: at birth
measure: small-for-gestational age newborn
timeFrame: at birth
measure: neonatal hypoglycemia
timeFrame: in the neonatal period
measure: perinatal mortality
timeFrame: in the perinatal period
measure: insulin treatment
timeFrame: from enrollment to delivery
Secondary outcomes:
measure: fasting blood glucose
timeFrame: in the period from enrollment to delivery
measure: postprandial blood glucose
timeFrame: in the period from enrollment to delivery
measure: maternal weight gain since enrollment
timeFrame: in the period from enrollment to delivery
measure: pregnancy-induced hypertension
timeFrame: during pregnancy
measure: induction of labour
timeFrame: at the end of pregnancy
measure: cord C peptide
timeFrame: at birth
measure: cord insulin
timeFrame: at birth
measure: abnormal 1 min Apgar
timeFrame: at birth
measure: abnormal 5 min Apgar
timeFrame: at birth
measure: obstetric trauma
timeFrame: at birth
measure: severe neonatal hypoglycemia
timeFrame: in the neonatal period
measure: neonatal jaundice
timeFrame: in the neonatal period
measure: significant respiratory distress
timeFrame: in the neonatal period
measure: stillbirth
timeFrame: in the antenatal period
measure: neonatal mortality
timeFrame: in the neonatal period
measure: Neonatal Intensive Care Unit (NICU) admittance
timeFrame: in the neonatal period
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
Study officials:
References:
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. doi: 10.1056/NEJM200010193431601.
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.
citation: 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.
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.
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.
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.
citation: Balsells M, Garcia-Patterson A, Sola I, Roque M, Gich I, Corcoy R. Glibenclamide, metformin, and insulin for the treatment of gestational diabetes: a systematic review and meta-analysis. BMJ. 2015 Jan 21;350:h102. doi: 10.1136/bmj.h102.