Gestational Diabetes MellitusNCT01998113
Glyburide and Metformin for the Treatment of Gestational Diabetes Mellitus. Systematic Review
An observational study of Gestational Diabetes Mellitus, run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau at 1 site in Spain.
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)… Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Gestational Diabetes Mellitus
- What is being tested?
- Glyburide vs Insulin trials, Metformin vs Insulin trials and Metformin vs Glyburide trials
- How many people
- 2,509 participants
- Where
- 1 siteSpain
- Study dates
- Mar 2013to May 2014
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Study population: pregnant women with gestational diabetes mellitus requiring drug treatment
Who may be able to join
- RCT
- GDM
- comparing Glyburide vs Insulin, Metformin vs Insulin or Metformin vs Glyburide
- data on fetal and/or maternal outcomes
- full text available
Who cannot join
- significant overlap with other articles of the same group
Trial locations and contacts
1 site in 1 country.
About this study
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.
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)
Read the 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.
- Conditions
- Gestational Diabetes Mellitus
- Being tested
- Glyburide vs Insulin trials, Metformin vs Insulin trials, Metformin vs Glyburide trials
- Keywords
- gestational diabetes mellitus, glyburide, metformin, oral agents, insulin, outcomes
- Medical subject headings
- Diabetes, Gestational, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Glyburide vs Insulin trialsDrug
Affecting groups 1 and 2
Metformin vs Insulin trialsDrug
Affecting groups 3 and 4
Metformin vs Glyburide trialsDrug
Affecting groups 5 and 6
| Study group | Role | What they receive |
|---|---|---|
| Glyburide (Glyburide vs Insulin) | Glyburide vs Insulin trials Receives: Drug: Glyburide vs Insulin trials | |
| Insulin (Glyburide vs Insulin) | Glyburide vs Insulin trials Receives: Drug: Glyburide vs Insulin trials | |
| Metformin (Metformin vs Insulin) | Metformin vs Insulin trials Receives: Drug: Metformin vs Insulin trials | |
| Insulin (Metformin vs Insulin) | Metformin vs Insulin trials Receives: Drug: Metformin vs Insulin trials | |
| Metformin (Metformin vs Glyburide) | Metformin vs Glyburide trials Receives: Drug: Metformin vs Glyburide trials | |
| Glyburide (Metformin vs Glyburide) | Metformin vs Glyburide trials Receives: Drug: Metformin vs Glyburide trials |
What is being measured
The primary outcome is the main question the study is designed to answer.
3rd trimester glycated hemoglobin
mean difference of 3rd trimester glycated hemoglobin
Measured: 3rd trimester of pregnancy
total maternal weight gain
mean difference of total maternal weight gain (as defined by the authors)
Measured: during pregnancy
severe maternal hypoglycemia
relative risk of severe maternal hypoglycemia (as defined by the authors)
Measured: from enrollment to delivery
preeclampsia
relative risk of preeclampsia (as defined by the authors)
Measured: during pregnancy or puerperium
cesarean section
relative risk of cesarean section (as defined by the authors)
Measured: at the end of pregnancy
gestational age at birth
mean difference of gestational age at birth (as defined by the authors)
Measured: at birth
preterm birth
relative risk of preterm birth (as defined by the authors)
Measured: at birth
birthweight
mean difference of birthweight (as defined by the authors)
Measured: at birth
macrosomia
relative risk of macrosomia (defined as birthweight >=4000 g)
Measured: at birth
large-for-gestational age newborn
relative risk of large-for-gestational age newborn (as defined by the authors)
Measured: at birth
small-for-gestational age newborn
relative risk of small-for-gestational age newborn (as defined by the authors)
Measured: at birth
neonatal hypoglycemia
relative risk of neonatal hypoglycemia (as provided by the authors)
Measured: in the neonatal period
perinatal mortality
relative risk of perinatal mortality (as defined by the authors)
Measured: in the perinatal period
insulin treatment
relative risk of insulin treatment (for trials comparing metformin vs glyburide)
Measured: from enrollment to delivery
Secondary outcomes (16)
fasting blood glucose
mean difference of fasting blood glucose (as defined by the authors)
Measured: in the period from enrollment to delivery
postprandial blood glucose
mean difference of postprandial blood glucose (as defined by the authors)
Measured: in the period from enrollment to delivery
maternal weight gain since enrollment
mean difference of maternal weight gain since enrollment (as defined by the authors)
Measured: in the period from enrollment to delivery
pregnancy-induced hypertension
relative risk of pregnancy-induced hypertension (as defined by the authors)
Measured: during pregnancy
induction of labour
relative risk of induction of labour (as described by the authors)
Measured: at the end of pregnancy
cord C peptide
mean difference of cord C peptide (as defined by the authors)
Measured: at birth
cord insulin
mean difference of cord insulin (as defined by the authors)
Measured: at birth
abnormal 1 min Apgar
relative risk of abnormal 1 min Apgar (defined as lower than 7)
Measured: at birth
abnormal 5 min Apgar
relative risk of abnormal 5 min Apgar (defined as lower than 7)
Measured: at birth
obstetric trauma
relative risk of obstetric trauma (as defined by the authors)
Measured: at birth
severe neonatal hypoglycemia
relative risk of severe neonatal hypoglycemia (as defined by the authors)
Measured: in the neonatal period
neonatal jaundice
relative risk of neonatal jaundice (as defined by the authors)
Measured: in the neonatal period
significant respiratory distress
relative risk of significant respiratory distress (described as respiratory distress syndrome or requiring respiratory support)
Measured: in the neonatal period
stillbirth
relative risk of stillbirth (as defined by the authors)
Measured: in the antenatal period
neonatal mortality
relative risk of neonatal mortality (as defined by the authors)
Measured: in the neonatal period
Neonatal Intensive Care Unit (NICU) admittance
relative risk of NICU admittance (as defined by the authors)
Measured: in the neonatal period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2013 (estimated)
- Study startMar 2013
- Primary completionMay 2014
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Gestational Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Time perspective
- Retrospective
- Enrolment
- 2,509 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01998113
- Sponsor's protocol ID
- IIBSP-ADO-2013-153
- Status last verified
- Nov 2013
- First submitted
- 8 Nov 2013
- Last updated
- 24 Mar 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 11036118Rowan 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.
PubMed 18463376Dhulkotia 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.
PubMed 20739011Nicholson 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.
PubMed 19104375Gui 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.
PubMed 23724063Silva 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.
PubMed 22505499Balsells 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.
PubMed 25609400
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01998113
- Acronym / sponsor ID
- IIBSP-ADO-2013-153
- Conditions
- Gestational Diabetes Mellitus
- Keywords
- gestational diabetes mellitus, glyburide, metformin, oral agents, insulin, outcomes
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 2,509 participants (actual)
- Lead sponsor
- Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauUniversity, hospital or other
- Study start
- Mar 2013
- Primary completion
- May 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 28 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Time perspective
- Retrospective
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Glyburide (Glyburide vs Insulin) | – | Drug: Glyburide vs Insulin trialsGlyburide vs Insulin trials |
| Insulin (Glyburide vs Insulin) | – | Drug: Glyburide vs Insulin trialsGlyburide vs Insulin trials |
| Metformin (Metformin vs Insulin) | – | Drug: Metformin vs Insulin trialsMetformin vs Insulin trials |
| Insulin (Metformin vs Insulin) | – | Drug: Metformin vs Insulin trialsMetformin vs Insulin trials |
| Metformin (Metformin vs Glyburide) | – | Drug: Metformin vs Glyburide trialsMetformin vs Glyburide trials |
| Glyburide (Metformin vs Glyburide) | – | Drug: Metformin vs Glyburide trialsMetformin vs Glyburide trials |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- pregnant women with gestational diabetes mellitus requiring drug treatment
Key inclusion criteria (5 listed)
- RCT
- GDM
- comparing Glyburide vs Insulin, Metformin vs Insulin or Metformin vs Glyburide
- data on fetal and/or maternal outcomes
- full text available
Key exclusion criteria (1 listed)
- significant overlap with other articles of the same group
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Glyburide vs Insulin trialsAffecting groups 1 and 2 | Drug | Glyburide (Glyburide vs Insulin), Insulin (Glyburide vs Insulin) |
| Metformin vs Insulin trialsAffecting groups 3 and 4 | Drug | Insulin (Metformin vs Insulin), Metformin (Metformin vs Insulin) |
| Metformin vs Glyburide trialsAffecting groups 5 and 6 | Drug | Glyburide (Metformin vs Glyburide), Metformin (Metformin vs Glyburide) |
Primary outcome
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)
16 secondary outcomes
fasting blood glucose
Time frame: in the period from enrollment to delivery
postprandial blood glucose
Time frame: in the period from enrollment to delivery
maternal weight gain since enrollment
Time frame: in the period from enrollment to delivery
pregnancy-induced hypertension
Time frame: during pregnancy
induction of labour
Time frame: at the end of pregnancy
cord C peptide
Time frame: at birth
cord insulin
Time frame: at birth
abnormal 1 min Apgar
Time frame: at birth
abnormal 5 min Apgar
Time frame: at birth
obstetric trauma
Time frame: at birth
severe neonatal hypoglycemia
Time frame: in the neonatal period
neonatal jaundice
Time frame: in the neonatal period
significant respiratory distress
Time frame: in the neonatal period
stillbirth
Time frame: in the antenatal period
neonatal mortality
Time frame: in the neonatal period
Neonatal Intensive Care Unit (NICU) admittance
Time frame: in the neonatal period
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2015.
- Background: PubMed 11036118Langer 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.
- Background: PubMed 18463376Rowan 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.
- Background: PubMed 20739011Dhulkotia 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.
- Background: PubMed 19104375Nicholson 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.
- Background: PubMed 23724063Gui 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.
- Background: PubMed 22505499Silva 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.
- Derived from this study: PubMed 25609400Balsells 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Gestational Diabetes Mellitus, run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
3rd trimester glycated hemoglobin (time frame: 3rd trimester of pregnancy). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01998113, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2015.