Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2017 Oct 18;10(10):CD007724.
doi: 10.1002/14651858.CD007724.pub3.

Oral anti-diabetic agents for women with established diabetes/impaired glucose tolerance or previous gestational diabetes planning pregnancy, or pregnant women with pre-existing diabetes

Joanna Tieu  1 , Suzette Coat, William Hague, Philippa Middleton, Emily Shepherd
Affiliations
Meta-Analysis

Oral anti-diabetic agents for women with established diabetes/impaired glucose tolerance or previous gestational diabetes planning pregnancy, or pregnant women with pre-existing diabetes

Joanna Tieu et al. Cochrane Database Syst Rev. .

Abstract

Background: While most guidance recommends the use of insulin in women whose pregnancies are affected by pre-existing diabetes, oral anti-diabetic agents may be more acceptable to women. The effects of these oral anti-diabetic agents on maternal and infant health outcomes need to be established in pregnant women with pre-existing diabetes or impaired glucose tolerance, as well as in women with previous gestational diabetes mellitus preconceptionally or during a subsequent pregnancy. This review is an update of a review that was first published in 2010.

Objectives: To investigate the effects of oral anti-diabetic agents in women with established diabetes, impaired glucose tolerance or previous gestational diabetes who are planning a pregnancy, or pregnant women with pre-existing diabetes, on maternal and infant health. The use of oral anti-diabetic agents for the management of gestational diabetes in a current pregnancy is evaluated in a separate Cochrane Review.

Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2016) and reference lists of retrieved studies.

Selection criteria: Randomised controlled trials (RCTs) and quasi-RCTs assessing the effects of oral anti-diabetic agents in women with established diabetes, impaired glucose tolerance or previous gestational diabetes who were planning a pregnancy, or pregnant women with pre-existing diabetes. Cluster-RCTs were eligible for inclusion, but none were identified.

Data collection and analysis: Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of the included RCTs. Review authors checked the data for accuracy, and assessed the quality of the evidence using the GRADE approach.

Main results: We identified six RCTs (707 women), eligible for inclusion in this updated review, however, three RCTs had mixed populations (that is, they included pregnant women with gestational diabetes) and did not report data separately for the relevant subset of women for this review. Therefore we have only included outcome data from three RCTs; data were available for 241 women and their infants. The three RCTs all compared an oral anti-diabetic agent (metformin) with insulin. The women in the RCTs that contributed data had type 2 diabetes diagnosed before or during their pregnancy. Overall, the RCTs were judged to be at varying risk of bias. We assessed the quality of the evidence for selected important outcomes using GRADE; the evidence was low- or very low-quality, due to downgrading because of design limitations (risk of bias) and imprecise effect estimates (for many outcomes only one or two RCTs contributed data).For our primary outcomes there was no clear difference between metformin and insulin groups for pre-eclampsia (risk ratio (RR) 0.63, 95% confidence interval (CI) 0.33 to 1.20; RCTs = 2; participants = 227; very low-quality evidence) although in one RCT women receiving metformin were less likely to have pregnancy-induced hypertension (RR 0.58, 95% CI 0.37 to 0.91; RCTs = 1; participants = 206; low-quality evidence). Women receiving metformin were less likely to have a caesarean section compared with those receiving insulin (RR 0.73, 95% CI 0.61 to 0.88; RCTs = 3; participants = 241; low-quality evidence). In one RCT there was no clear difference between groups for large-for-gestational-age infants (RR 1.12, 95% CI 0.73 to 1.72; RCTs = 1; participants = 206; very low-quality evidence). There were no perinatal deaths in two RCTs (very low-quality evidence). Neonatal mortality or morbidity composite outcome and childhood/adulthood neurosensory disability were not reported.For other secondary outcomes we assessed using GRADE, there were no clear differences between metformin and insulin groups for induction of labour (RR 1.42, 95% CI 0.62 to 3.28; RCTs = 2; participants = 35; very low-quality evidence), though infant hypoglycaemia was reduced in the metformin group (RR 0.34, 95% CI 0.18 to 0.62; RCTs = 3; infants = 241; very low-quality evidence). Perineal trauma, maternal postnatal depression and postnatal weight retention, and childhood/adulthood adiposity and diabetes were not reported.

Authors' conclusions: There are insufficient RCT data to evaluate the use of oral anti-diabetic agents in women with established diabetes, impaired glucose tolerance or previous gestational diabetes who are planning a pregnancy, or in pregnant women with pre-existing diabetes. Low to very low-quality evidence suggests possible reductions in pregnancy-induced hypertension, caesarean section birth and neonatal hypoglycaemia with metformin compared with insulin for women with type 2 diabetes diagnosed before or during their pregnancy, and no clear differences in pre-eclampsia, induction of labour and babies that are large-for-gestational age. Further high-quality RCTs that compare any combination of oral anti-diabetic agent, insulin and dietary and lifestyle advice for these women are needed. Future RCTs could be powered to evaluate effects on short- and long-term clinical outcomes; such RCTs could attempt to collect and report on the standard outcomes suggested in this review. We have identified three ongoing studies and four are awaiting classification. We will consider these when this review is updated.

PubMed Disclaimer

Conflict of interest statement

Joanna Tieu is supported by an NHMRC postgraduate scholarship and Arthritis Australia Ken Muirden fellowship (jointly funded by the Australian Rheumatology Association and Roche).

Suzette Coat is involved in the conduct of the Treatment of Booking Gestational diabetes Mellitus Study (TOBoGM), Bishop 2017. This study seeks to determine whether diagnosis and treatment of gestational diabetes mellitus in the first trimester in women with risk factors for overt diabetes is beneficial to the woman and her fetus/baby.

William Hague: I am a chief investigator (CIB) for the Treatment of Booking GDM trial (TOBoGM), Bishop 2017, currently funded by a NHMRC project grant. I was an AI in the Mothers After Gestational Diabetes in Australia (MAGDA) study (O'Reilly 2016), and also a co‐author on some of the work by Van Ryswyk 2016, which impinge on this review. This was taken into account when writing the review.

Philippa Middleton: none known.

Emily Shepherd: none known.

Figures

1
1
Study flow diagram
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
1.1
1.1. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 1 Hypertensive disorders of pregnancy: pre‐eclampsia.
1.2
1.2. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 2 Hypertensive disorders of pregnancy: pregnancy‐induced hypertension.
1.3
1.3. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 3 Caesarean section.
1.4
1.4. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 4 Large‐for‐gestational age.
1.5
1.5. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 5 Perinatal mortality.
1.6
1.6. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 6 Miscarriage.
1.7
1.7. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 7 Induction of labour.
1.8
1.8. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 8 Postpartum haemorrhage.
1.9
1.9. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 9 Weight gain in pregnancy (kg).
1.11
1.11. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 11 Adherence to the intervention (how often did you forget to take treatment?).
1.12
1.12. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 12 Adherence to the intervention.
1.13
1.13. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 13 Views of the intervention (which medication would you choose in next pregnancy?).
1.14
1.14. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 14 Views of the intervention (which part of diabetes treatment was easy?).
1.15
1.15. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 15 Views of the intervention (which part of diabetes treatment was difficult?).
1.16
1.16. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 16 Views of the intervention (choose same treatment in the future).
1.17
1.17. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 17 Adverse effects of the intervention (side effects).
1.18
1.18. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 18 Breastfeeding.
1.19
1.19. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 19 Glycaemic control (fasting blood glucose throughout pregnancy (mg/dL)).
1.20
1.20. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 20 Glycaemic control (random blood glucose throughout pregnancy (mg/dL)).
1.21
1.21. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 21 Glycaemic control (change in HbA1c from enrolment to third trimester/birth (%)).
1.22
1.22. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 22 Glycaemic control (HbA1c < 7% at third trimester/birth).
1.24
1.24. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 24 Congenital anomaly (major malformations).
1.25
1.25. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 25 Stillbirth.
1.26
1.26. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 26 Neonatal mortality.
1.27
1.27. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 27 Gestational age at birth (weeks).
1.29
1.29. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 29 Preterm birth.
1.30
1.30. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 30 Apgar score < 7 at 5 minutes.
1.31
1.31. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 31 Macrosomia (> 4000 g).
1.32
1.32. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 32 Small‐for‐gestational age.
1.33
1.33. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 33 Birthweight (kg).
1.37
1.37. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 37 Shoulder dystocia.
1.38
1.38. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 38 Bone fracture (birth injury/birth trauma with clavicle fracture).
1.39
1.39. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 39 Respiratory distress syndrome.
1.40
1.40. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 40 Hypoglycaemia.
1.41
1.41. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 41 Hyperbilirubinaemia (jaundice).
1.42
1.42. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 42 Infection (sepsis).
1.43
1.43. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 43 Relevant biomarkers (blood glucose level at birth (mg/dL)).
1.45
1.45. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 45 Number of antenatal admissions.
1.46
1.46. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 46 Neonatal intensive care unit admission.
1.48
1.48. Analysis
Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 48 Cost of maternal care (total cost of treatment throughout pregnancy (USD)).
See this image and copyright information in PMC

Update of

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

References to studies included in this review

Ainuddin 2015 {published data only}
    1. Ainuddin JA, Karim N, Zaheer S, Ali SS, Hasan AA. Metformin treatment in type 2 diabetes in pregnancy: an active controlled, parallel‐group, randomized, open label study in patients with type 2 diabetes in pregnancy. Journal of Diabetes Research 2015;2015:325851. - PMC - PubMed
    1. NCT01855763. Metformin in gestational diabetes and type 2 diabetes in pregnancy in a developing country. clinicaltrials.gov/ct2/show/NCT01855763 (first received 9 May 2013).
Beyuo 2015 {published data only}
    1. Beyuo T, Obed SA, Adjepong‐Yamoah KK, Bugyei KA, Oppong SA, Marfoh K. Metformin versus insulin in the management of pre‐gestational diabetes mellitus in pregnancy and gestational diabetes mellitus at the Korle Bu Teaching Hospital: a randomized clinical trial. PLOS ONE 2015;10(5):e0125712. - PMC - PubMed
Hickman 2013 {published data only}
    1. Hickman MA, McBride R, Boggess KA, Strauss R. Metformin compared with insulin in the treatment of pregnant women with overt diabetes: a randomized controlled trial. American Journal of Perinatology 2013;30(6):483‐90. - PubMed
    1. NCT00835861. Effectiveness of metformin compared to insulin in pregnant women with mild preexisting or early gestational diabetes (MIPOD). clinicaltrials.gov/ct2/show/results/NCT00835861 (first received 2 February 2009).
Ibrahim 2014 {published data only}
    1. Ibrahim MI, Hamdy A, Shafik A, Taha S, Anwar M, Faris M. The role of adding metformin in insulin‐resistant diabetic pregnant women: a randomized controlled trial. Archives of Gynecology and Obstetrics 2014;289(5):959‐65. - PubMed
    1. NCT01915550. The role of adding metformin in insulin‐resistant diabetic pregnant women ‐ a randomized controlled trial. clinicaltrials.gov/ct2/show/NCT01915550 (first received 2 August 2013).
Notelovitz 1971 {published data only}
    1. Notelovitz M. Sulphonylurea therapy in the treatment of the pregnant diabetic. South African Medical Journal 1971;45:226‐9. - PubMed
Refuerzo 2015 {published data only}
    1. NCT00678080. Metformin versus insulin in pregnant women with type 2 diabetes. clinicaltrials.gov/ct2/show/NCT00678080 (first received 8 May 2008).
    1. Refuerzo JS, Gowen R, Pedroza C, Hutchinson M, Blackwell SC, Ramin S. A pilot randomized, controlled trial of metformin versus insulin in women with type 2 diabetes mellitus during pregnancy. American Journal of Perinatology 2015;32(2):163‐70. - PubMed

References to studies excluded from this review

Anjalakshi 2007 {published data only}
    1. Anjalakshi C, Balaji V, Balaji MS, Seshiah V. A prospective study comparing insulin and glibenclamide in gestational diabetes mellitus in Asian Indian women. Diabetes Research and Clinical Practice 2007;76(3):474‐5. - PubMed
Bertini 2005 {published data only}
    1. Bertini AM, Silva JC, Taborda W, Becker F, Bebber FR, Viesi JM, et al. Perinatal outcomes and the use of oral hypoglycemic agents. Journal of Perinatal Medicine 2005;33(6):519‐23. - PubMed
Carlsen 2007 {published data only}
    1. Carlsen SM, Kjotrod S, Vanky E, Romundstad P. Homocysteine levels are unaffected by metformin treatment in both nonpregnant and pregnant women with polycystic ovary syndrome. Acta Obstetricia et Gynecologica Scandinavica 2007;86(2):145‐50. - PubMed
Casey 2015 {published data only}
    1. Casey BM, Duryea EL, Abbassi‐Ghanavati M, Tudela CM, Shivvers SA, McIntire DD, et al. Glyburide in women with mild gestational diabetes: a randomized controlled trial. Obstetrics and Gynecology 2015;126(2):303‐9. - PubMed
Corrado 2011 {published data only}
    1. Corrado F, D'Anna R, di G, Giordano D, Pintaudi B, Santamaria A, et al. The effect of myoinositol supplementation on insulin resistance in patients with gestational diabetes. Diabetic Medicine 2011;28(8):972‐5. - PubMed
George 2015 {published data only}
    1. George A, Mathews JE, Sam D, Beck M, Benjamin SJ, Abraham A, et al. Comparison of neonatal outcomes in women with gestational diabetes with moderate hyperglycaemia on metformin or glibenclamide ‐ a randomised controlled trial. Australian & New Zealand Journal of Obstetrics & Gynaecology 2015;55(1):47‐52. - PubMed
Golladay 2005 {published data only}
    1. NCT00160485. Glyburide compared to insulin in the management of White's classification A2 gestational diabetes. clinicaltrials.gov/ct2/show/NCT00160485 (first received 8 September 2005).
Hague 2003 {published data only}
    1. Hague WM, Davoren PM, Oliver J, Rowan J. Contraindications to use of metformin. Metformin may be useful in gestational diabetes [comment]. BMJ 2003; Vol. 326:762. - PubMed
Hague 2010 {published data only}
    1. ACTRN12610000157077. Metformin in the prevention of gestational diabetes: the MPG trial. anzctr.org.au/trial_view.aspx?ID=320961 (first received 16 February 2010).
Langer 2000b {published data only}
    1. Langer O, Conway D, Berkus M, Xenakis EM. Oral hypoglycaemic agent is comparable to insulin in GDM management. American Journal of Obstetrics and Gynecology 1999;180(1 Pt 2):S6.
    1. Langer O, Conway DL, Berkus MD, Xenakis EM, Gonzales O. A comparison of glyburide and insulin in women with gestational diabetes mellitus. New England Journal of Medicine 2000;343(16):1134‐8. - PubMed
    1. Langer O, Yogev Y, Brustman L, Rosenn B. Is there a relationship between severity of gestational diabetes (GDM) and pregnancy outcome in insulin‐ and glyburide‐treated patients?. American Journal of Obstetrics and Gynecology 2003;189(6 Suppl 1):S105.
    1. Langer O, Yogev Y, Rosenn B, Brustman L. Glyburide therapy: the relationship between dosage and level of gestational diabetes (GDM) severity. American Journal of Obstetrics and Gynecology 2003;189(6 Suppl 1):S105. - PubMed
    1. Langer O, Yogev Y, Xenakis EM, Rosenn B. Insulin and glyburide therapy: dosage, severity level of gestational diabetes, and pregnancy outcome. American Journal of Obstetrics and Gynecology 2005;192(1):134‐9. - PubMed
Martinez 2010 {published data only}
    1. Martinez P, Abdulhaj Martinez M, Andres Nunez P, Garcia Leon P, Lopez Sanchez EJ, Gonzalez Ramirez AR. A randomized study comparing metformin and insulin in the treatment of gestational diabetes mellitus. Interim results. Journal of Maternal‐Fetal and Neonatal Medicine 2010;23(S1):381.
Moore 2005 {published data only}
    1. Moore L, Clokey D, Robinson A. A randomized trial of metformin compared to glyburide in the treatment of gestational diabetes. American Journal of Obstetrics and Gynecology 2005;193(6 Suppl):S92.
Moore 2007 {published data only}
    1. Moore L, Briery C, Martin R, Hood E, Bofill J, Morrison J. Metformin (M) vs. insulin (I) in A2 diabetes: a randomized clinical trial [abstract]. American Journal of Obstetrics and Gynecology 2004;191(6 Suppl 1):S8.
    1. Moore LE, Briery CM, Clokey D, Martin RW, Williford NJ, Bofill JA, et al. Metformin and insulin in the management of gestational diabetes mellitus: preliminary results of a comparison. Journal of Reproductive Medicine 2007;52(11):1011‐5. - PubMed
Mukhopadhyay 2012 {published data only}
    1. Mukhopadhyay P, Bag TS, Kyal A, Saha DP, Khalid N. Oral hypoglycemic glibenclamide: can it be a substitute to insulin in the management of gestational diabetes mellitus? A comparative study. Journal of South Asian Federation of Obstetrics and Gynaecology (SAFOG) 2012;4(1):28‐31.
Myers 2013 {published data only}
    1. ISRCTN86503951. Management of mild gestational diabetes mellitus (GDM). isrctn.com/ISRCTN86503951 (first received 23 December 2013).
Niromanesh 2012 {published data only}
    1. IRCT201105075591N2. Metformin compared with insulin in control of blood sugar in gestational diabetes mellitus. en.search.irct.ir/view/5930 (first received 31 March 2011).
    1. Niromanesh S, Alavi A, Sharbaf FR, Amjadi N, Moosavi S, Akbari S. Metformin compared with insulin in the management of gestational diabetes mellitus: a randomized clinical trial. Diabetes Research and Clinical Practice 2012;98(3):422‐9. - PubMed
Rowan 2008b {published data only}
    1. Rowan J. A trial in progress: gestational diabetes. Diabetes Care 2007;30:S214‐S219. - PubMed
    1. Rowan J. Metformin in gestational diabetes: follow up of offspring of mothers treated with insulin compared with metformin. anzctr.org.au/Trial/Registration/TrialReview.aspx?id=335 (first received 6 September 2005).
    1. Rowan JA, Gao W, Hague WM, McIntyre HD. Glycemia and its relationship to outcomes in the metformin in gestational diabetes trial. Diabetes Care 2010;33(1):9‐16. - PMC - PubMed
    1. Rowan JA, Hague WM, Gao W, Battin MR, Moore MP, for the MiG Trial Investigators. Metformin versus insulin for the treatment of gestational diabetes. New England Journal of Medicine 2008;358(19):2003‐15. - PubMed
    1. Rowan JA, Rush EC, Obolonkin V, Battin M, Wouldes T, Hague WM. Metformin in gestational diabetes: the offspring follow‐up (MiG TOFU): body composition at 2 years of age. Diabetes Care 2011;34(10):2279‐84. - PMC - PubMed
Singh 2011 {published data only}
    1. CTRI/2011/08/001956. Can oral medication replace insulin injections in pregnant women with diabetes. ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=3378 (first received 19 August 2011).
Vanky 2004 {published data only}
    1. Salvesen KA, Vanky E, Carlsen SM. Metformin treatment in pregnant women with polycystic ovary syndrome ‐ is reduced complication rate mediated by changes in the uteroplacental circulation?. Ultrasound in Obstetrics and Gynecology 2007;29(4):433‐7. - PubMed
    1. Vanky E, Salvesen KA, Bjerve K, Carlsen SM. C‐Reactive protein in metformin treated pregnant PCOS women. XXXIV Congress of Nordic Federation of Societies of Obstetrics and Gynecology; 2004 June 12‐15;Helsinki, Finland. 2004:76.
    1. Vanky E, Salvesen KA, Heimstad R, Fougner KJ, Romundstad P, Carlsen SM. Metformin reduces pregnancy complications without affecting androgen levels in pregnant polycystic ovary syndrome women: results of a randomized study. Human Reproduction 2004;19(8):1734‐40. - PubMed
    1. Vanky E, Salvesen KA, Hjorth‐Hansen H, Bjerve K, Carlsen SM. Beneficial effect of metformin on pregnancy outcome in women with polycystic ovary syndrome is not associated with major changes in C‐reactive protein levels or indices of coagulation. Fertility & Sterility 2006;85(3):770‐4. - PubMed
Vanky 2005 {published data only}
    1. NCT00159536. Metformin in pregnant PCOS women. clinicaltrials.gov/ct2/show/NCT00159536 (first received 8 September 2005).
Wali 2012 {published data only}
    1. ACTRN12612001272886. A phase three open label randomized controlled trial to compare the efficacy of oral hypoglycemic agents (OHA) with insulin in the treatment of gestational diabetes mellitus (GDM). anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363218 (first received 7 December 2012).
Zanganeh 2010 {published data only}
    1. Zangeneh M. The comparative study of therapeutic effects of insulin and glibenclamide in the gestational diabetes mellitus. http://en.search.irct.ir/view/4374 (first received 1 December 2010).

References to studies awaiting assessment

Coiner 2014 {published data only}
    1. Coiner J, Rowe M, DeVente J. The treatment of diabetes in pregnancy; metformin vs glyburide and insulin biomedical evidence of fetopathy. American Journal of Obstetrics and Gynecology 2014; Vol. 210, issue 1 Suppl 1:S148.
Hutchinson 2008 {published data only (unpublished sought but not used)}
    1. Hutchinson A, Haugabrook C, Long L, Mason L, Kipikasa J, Adair D. A comparison of glyburide/metformin and insulin for gestational diabetes. American Journal of Obstetrics and Gynecology 2008;199(6 Suppl 1):S200.
    1. NCT00371306. Comparison of glucovance to insulin for diabetes during pregnancy. clinicaltrials.gov/ct2/show/NCT00371306 (first received 1 September 2006).
Reyes‐Munoz 2014 {published data only}
    1. Reyes‐Munoz E, Ortega‐Gonzalez C, Mier‐Cabrera J, Avila‐Carrasco A, Espino S, Ayala‐Yanez R. Medical nutrition therapy plus metformin for preventing gestational diabetes among high‐risk women. Obstetrics and Gynecology 2014;123 Suppl 1:168S.
Waheed 2013 {published data only}
    1. Waheed S, Malik FP, Mazhar SB. Efficacy of metformin versus insulin in the management of pregnancy with diabetes. Journal of the College of Physicians and Surgeons‐‐Pakistan 2013;23(12):866‐9. - PubMed

References to ongoing studies

Feig 2011 {published data only}
    1. Feig DS, Murphy K, Asztalos E, Tomlinson G, Sanchez J, Zinman B, et al. Metformin in women with type 2 diabetes in pregnancy (MiTy): a multi‐center randomized controlled trial. BMC Pregnancy and Childbirth 2016;16(1):173. - PMC - PubMed
    1. NCT01353391. Metformin in women with type 2 diabetes in pregnancy a randomized controlled trial. clinicaltrials.gov/ct2/show/NCT01353391 (first received 2 May 2011).
Sheizaf 2006 {published data only}
    1. NCT00414245. Metformin for the treatment of diabetes in pregnancy. clinicaltrials.gov/ct2/show/record/NCT00414245 (first received 20 December 2006).
Van der Linden 2014 {published data only}
    1. NCT02275845. Metformin vs control to prevent gestational diabetes mellitus (GDM) in women with a high risk for GDM, an open label randomized controlled trial. The Medico‐GDM trial. clinicaltrials.gov/ct2/show/NCT02275845 (first received 23 October 2014).

Additional references

ADA 2015
    1. American Diabetes Association. Management of diabetes in pregnancy. Diabetes Care 2015;38(Suppl 1):S77‐S79. - PubMed
ADIPS 2005
    1. McElduff A, Cheung NW, McIntyre HD, Lagstrom JA, Oats JJ, Ross GP, et al. The Australasian Diabetes in Pregnancy Society consensus guidelines for the management of type 1 and type 2 diabetes in relation to pregnancy. Medical Journal of Australia 2005;183(7):373‐7. - PubMed
Alwan 2009
    1. Alwan N, Tuffnell DJ, West J. Treatments for gestational diabetes. Cochrane Database of Systematic Reviews 2009, Issue 3. [DOI: 10.1002/14651858.CD003395.pub2] - DOI - PMC - PubMed
Bell 2008
    1. Bell R, Bailey K, Cresswell T, Hawthorne G, Critchley J, Lewis‐Barned N, et al. Trends in prevalence and outcomes of pregnancy in women with pre‐existing type I and type II diabetes. BJOG: an international journal of obstetrics and gynaecology 2008;115(4):445‐52. - PubMed
Bishop 2017
    1. Bishop C, Simmons D. The Treatment Of BOoking Gestational diabetes Mellitus Study: Evaluating the impact on obstetric outcomes of immediate versus delayed care for gestational diabetes diagnosed at booking. http://www.anzctr.org.au/ACTRN12616000924459.aspx 2017. [ACTRN12616000924459]
Brock 2005
    1. Brock B, Smidt K, Ovesen P, Schmitz O, Rungby J. Is metformin therapy for polycystic ovary syndrome safe during pregnancy?. Basic & Clinical Pharmacology & Toxicology 2005;96:410‐2. - PubMed
Brown 2016a
    1. Brown J, Crawford TJ, Alsweiler J, Crowther CA. Dietary supplementation with myo‐inositol in women during pregnancy for treating gestational diabetes. Cochrane Database of Systematic Reviews 2016, Issue 9. [DOI: 10.1002/14651858.CD012048.pub2] - DOI - PMC - PubMed
Brown 2016b
    1. Brown J, Grzeskowiak L, Williamson K, Downie MR, Crowther CA. Insulin for the treatment of women with gestational diabetes. Cochrane Database of Systematic Reviews 2016, Issue 1. [DOI: 10.1002/14651858.CD012037] - DOI - PMC - PubMed
Brown 2017a
    1. Brown J, Alwan NA, West J, Brown S, McKinlay CJ, Farrar D, et al. Lifestyle interventions for the treatment of women with gestational diabetes. Cochrane Database of Systematic Reviews 2017, Issue 5. [DOI: 10.1002/14651858.CD011970.pub2] - DOI - PMC - PubMed
Brown 2017b
    1. Brown J, Martis R, Hughes B, Rowan J, Crowther CA. Oral anti‐diabetic pharmacological therapies for the treatment of women with gestational diabetes. Cochrane Database of Systematic Reviews 2017, Issue 1. [DOI: 10.1002/14651858.CD011967.pub2] - DOI - PMC - PubMed
Butalia 2017
    1. Butalia S, Gutierrez L, Lodha A, Aitken E, Zakariasen A, Donovan L. Short‐ and long‐term outcomes of metformin compared with insulin alone in pregnancy: a systematic review and meta‐analysis. Diabetic Medicine 2017;34(1):27‐36. - PubMed
CDA 2013
    1. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee, Canadian Diabetes Association. 2013 Clinical Practice Guidelines for the prevention and management of diabetes in Canada. Canadian Journal of Diabetes 2013;37(Suppl 1):S1‐S212. - PubMed
Chan 2005
    1. Chan LYS, Yeung JH, Lau TK. Placental transfer of rosiglitazone in the first trimester of human pregnancy. Fertility and Sterility 2005;83(4):955‐8. - PubMed
Coetzee 2007
    1. Coetzee EJ. Counterpoint: oral hypoglycemic agents should be used to treat diabetic pregnant women. Diabetes Care 2007;30:2980‐2. - PubMed
Correa 2015
    1. Correa A, Bardenheier B, Elixhauser A, Geiss LS, Gregg E. Trends in prevalence of diabetes among delivery hospitalizations, United States, 1993–2009. Maternal and Child Health Journal 2015;19:635‐42. - PMC - PubMed
Crowther 2005
    1. Crowther C, Hiller J, Moss J, McPhee A, Jeffries W, Robinson J, et al. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. New England Journal of Medicine 2005;352:2477‐86. - PubMed
Dabelea 2000
    1. Dabelea D, Knowler WC, Pettitt DJ. Effect of diabetes in pregnancy on offspring: follow‐up research in the Pima Indians. Journal of Maternal‐Fetal Medicine 2000;9:83‐8. - PubMed
DeFronzo 1984
    1. DeFronzo RA, Simonson DC. Oral sulfonylurea agents suppress hepatic glucose production in non‐insulin‐dependent diabetic individuals. Diabetes Care 1984;7(Suppl 1):72‐80. - PubMed
DeFronzo 1995
    1. DeFronzo RA, Goodman AM, the Multicenter Metformin Study Group. Efficacy of metformin in patients with non‐insulin‐dependent diabetes mellitus. New England Journal of Medicine 1995;333(9):541‐9. - PubMed
Ekpebegh 2007
    1. Ekpebegh CO, Coetzee EJ, Merwe L, Levitt NS. A 10‐year retrospective analysis of pregnancy outcome in pregestational type 2 diabetes: comparison of insulin and oral glucose‐lowering agents. Diabetic Medicine 2007;24:253‐8. - PubMed
Farrar 2016
    1. Farrar D, Tuffnell DJ, West J, West HM. Continuous subcutaneous insulin infusion versus multiple daily injections of insulin for pregnant women with diabetes. Cochrane Database of Systematic Reviews 2016, Issue 6. [DOI: 10.1002/14651858.CD005542.pub3] - DOI - PMC - PubMed
Glueck 2004
    1. Glueck CJ, Goldenberg N, Pranikoff J, Lotspring M, Sieve L, Wang P. Height, weight, and motor‐social development during the first 18 months of life in 126 infants born to 109 mothers with polycystic ovary syndrome who conceived on and continued metformin through pregnancy. Human Reproduction 2004;19(6):1323‐30. - PubMed
Gutzin 2003
    1. Gutzin SJ, Kozer E, Magee LA, Feig DS, Koren G. The safety of oral hypoglycemic agents in the first trimester of pregnancy: a meta‐analysis. Canadian Journal of Clinical Pharmacology 2003;10(4):179‐83. - PubMed
Hellmuth 2000
    1. Hellmuth E, Damm P, Molsted‐Pedersen L. Oral hypoglycaemic agents in 118 diabetic pregnancies. Diabetic Medicine 2000;17(7):507‐11. - PubMed
Higgins 2011
    1. Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Ho 2007
    1. Ho FL, Liew CF, Cunanan EC, Lee KO. Oral hypoglycaemic agents for diabetes in pregnancy: an appraisal of the current evidence for oral anti‐diabetic drug use in pregnancy. Annals of the Academy of Medicine, Singapore 2007;36:672‐8. - PubMed
Homko 2006
    1. Homko CJ, Reece EA. Insulins and oral hypoglycemic agents in pregnancy. Journal of Maternal‐Fetal and Neonatal Medicine 2006;19(11):679‐86. - PubMed
IDF 2015
    1. International Diabetes Federation (IDF). IDF Diabetes Atlas. 7th Edition. Brussels: International Diabetes Federation, 2015.
Jensen 2004
    1. Jensen DM, Dam P, Moelsted‐Pedersen L, Ovesen P, Westergaard JG, Moeller M, et al. Outcomes in type 1 diabetic pregnancies. Diabetes Care 2004;27(12):2819‐23. - PubMed
Jiwani 2012
    1. Jiwani A, Marseille E, Lohse N, Damm P, Hod M, Kahn JG. Gestational diabetes mellitus: results from a survey of country prevalence and practices. Journal of Maternal Fetal and Neonatal Medicine 2012;25(6):600‐10. - PubMed
Jovanovic 2007
    1. Jovanovic L. Point: oral hypoglycemic agents should not be used to treat diabetic pregnant women. Diabetes Care 2007;30:2976‐9. - PubMed
Khambalia 2013
    1. Khambalia AZ, Ford JB, Nassar N, Shand AW, McElduff A, Roberts CL. Occurrence and recurrence of diabetes in pregnancy. Diabetic Medicine 2013;30:452‐6. - PubMed
Kim 2002
    1. Kim C, Newton KM, Knopp RH. Gestational diabetes and the incidence of type 2 diabetes: a systematic review. Diabetes Care 2002;25:1862‐8. - PubMed
Kim 2007
    1. Kim C, Berger DK, Chamany S. Recurrence of gestational diabetes mellitus: a systematic review. Diabetes Care 2007;30:1314‐9. - PubMed
Kitzmiller 1996
    1. Kitzmiller JL, Buchanan TA, Kjos S, Combs CA, Ratner RE. Pre‐conception care of diabetes, congenital malformations, and spontaneous abortions. Diabetes Care 1996;19(5):514‐41. - PubMed
Kovo 2007
    1. Kovo M, Haroutinunian S, Feldman N, Hoffman A, Glezerman M. Determination of metformin transfer across the human placenta using a dually perfused ex vivo placental cotelydon model. European Journal of Obstetrics & Gynecology and Reproductive Biology 2008;136(1):29‐33. - PubMed
Kraemer 2006
    1. Kraemer J, Klein J, Lubetsky A, Koren G. Perfusion studies of glyburide transfer across the human placenta: implications for fetal safety. American Journal of Obstetrics and Gynecology 2006;195(1):270‐4. - PubMed
Landon 2009
    1. Landon MB, Spong CY, Thorn E, Carpenter MW, Ramin SM, Casey B, et al. A multicenter, randomized trial of treatment for mild gestational diabetes. New England Journal of Medicine 2009;361(14):1339‐48. - PMC - PubMed
Langer 2000a
    1. Langer O, Conway DL, Berkus MD, Xenakis EM, Gonzales O. A comparison of glyburide and insulin in women with gestational diabetes mellitus. New England Journal of Medicine 2000;343(16):1134‐8. - PubMed
Lawrence 2008
    1. Lawrence JM, Contreras R, Chen W, Sacks DA. Trends in the prevalence of preexisting diabetes and gestational diabetes mellitus among a racially/ethnically diverse population of pregnant women, 1999‐2005. Diabetes Care 2008;31(5):899‐904. - PubMed
Leguizamon 2007
    1. Leguizamon G, Igarzabal ML, Reece EA. Preconceptional care of women with diabetes mellitus. Obstetrics and Gynecology Clinics of North America 2007;34(2):225‐39. - PubMed
Macintosh 2006
    1. Macintosh MC, Fleming KM, Bailey JA, Doyle P, Modder J, Acolet D, et al. Perinatal mortality and congenital anomalies in babies of women with type 1 or type 2 diabetes in England, Wales, and Northern Ireland: population based study. BMJ 2006;333(7560):177. - PMC - PubMed
Mahmud 2010
    1. Mahmud M, Mazza D. Preconception care of women with diabetes: a review of current guideline recommendations. BMC Women's Health 2010;10:5. - PMC - PubMed
Martis 2016
    1. Martis R, Brown J, Alsweiler J, Crawford TJ, Crowther CA. Different intensities of glycaemic control for women with gestational diabetes mellitus. Cochrane Database of Systematic Reviews 2016, Issue 4. [DOI: 10.1002/14651858.CD011624.pub2] - DOI - PMC - PubMed
Middleton 2016
    1. Middleton P, Crowther CA, Simmonds L. Different intensities of glycaemic control for pregnant women with pre‐existing diabetes. Cochrane Database of Systematic Reviews 2016, Issue 5. [DOI: 10.1002/14651858.CD008540.pub4] - DOI - PMC - PubMed
Moy 2014
    1. Moy FM, Ray A, Buckley BS. Techniques of monitoring blood glucose during pregnancy for women with pre‐existing diabetes. Cochrane Database of Systematic Reviews 2014, Issue 4. [DOI: 10.1002/14651858.CD009613.pub2] - DOI - PubMed
NCT01832181
    1. NCT01832181. Metformin in women with type 2 diabetes in pregnancy kids trial (MiTy Kids). clinicaltrials.gov/ct2/show/NCT01832181 (first received 8 April 2013).
NICE 2015
    1. National Institute for Health and Clinical Excellence. Diabetes in pregnancy: management from preconception to the postnatal period. London: NICE, 2015. - PubMed
Nissen 2007
    1. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. New England Journal of Medicine 2007;356:2457‐71. - PubMed
O'Neill 2017
    1. O'Neill SM, Kenny LC, Khashan AS, West HM, Smyth RM, Kearney PM. Different insulin types and regimens for pregnant women with pre‐existing diabetes. Cochrane Database of Systematic Reviews 2017, Issue 2. [DOI: 10.1002/14651858.CD011880.pub2] - DOI - PMC - PubMed
O'Reilly 2016
    1. O'Reilly SL, Dunbar JA, Versace V, Janus E, Best JD, et al. MAGDA Study Group. Mothers after Gestational Diabetes in Australia (MAGDA): A Randomised Controlled Trial of a Postnatal Diabetes Prevention Program. PLoS Med 2016;13(7):e1002092. [DOI: 10.1371/journal.pmed.1002092] - DOI - PMC - PubMed
Ray 2001
    1. Ray JG, Vermeulen MJ, Shapiro JL, Kenshole AB. Maternal and neonatal outcomes in pregestational and gestational diabetes mellitus, and the influence of maternal obesity and weight gain: the DEPOSIT study. Quarterly Journal of Medicine 2001;94:347‐56. - PubMed
Reece 2010
    1. Reece EA. The fetal and maternal consequences of gestational diabetes mellitus. Journal of Maternal‐Fetal and Neonatal Medicine 2010;23(3):199‐203. - PubMed
RevMan 2014 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager 5 (RevMan 5). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Rowan 2008a
    1. Rowan JA, Hague WM, Gao W, Battin MR, Moore MP, MiG Trial Investigators. Metformin versus insulin for the treatment of gestational diabetes. New England Journal of Medicine 2008;358(19):2003‐15. - PubMed
Sheth 2002
    1. Sheth B. Does pregnancy accelerate the rate of progression of diabetic retinopathy?. Current Diabetes Report 2002;23(8):327‐30. - PubMed
Simonson 1984
    1. Simonson DC, Ferrannini E, Bevilacqua S, Smith D, Barrett E, Carlson R, et al. Mechanism of improvement of glucose metabolism after chronic glyburide therapy. Diabetes 1984;33(9):838‐45. - PubMed
Sivan 1995
    1. Sivan E, Feldman B, Dolitzki M, Nevo N, Dekel N, Karasik A. Glyburide crosses the placenta in vivo in pregnant rats. Diabetologia 1995;38(7):753‐6. - PubMed
Slocum 2002
    1. Slocum JM, Sosa MEB. Use of antidiabetes agents in pregnancy: current practice and controversy. Journal of Perinatal and Neonatal Nursing 2002;16(2):40‐53. - PubMed
Stumvoll 1995
    1. Stumvoll M, Nurjhan N, Perriello G, Dailey G, Gerich JE. Metabolic effects of metformin in non‐insulin‐dependent diabetes mellitus. New England Journal of Medicine 1995;333(9):588‐9. - PubMed
Tieu 2013
    1. Tieu J, Bain E, Middleton P, Crowther CA. Interconception care for women with a history of gestational diabetes for improving maternal and infant outcomes. Cochrane Database of Systematic Reviews 2013, Issue 6. [DOI: 10.1002/14651858.CD010211.pub2] - DOI - PubMed
Tieu 2017
    1. Tieu J, Middleton P, Crowther CA, Shepherd E. Preconception care for diabetic women for improving maternal and infant health. Cochrane Database of Systematic Reviews 2017, Issue 8. [DOI: 10.1002/14651858.CD007776.pub3] - DOI - PMC - PubMed
Van Ryswyk 2016
    1. Ryswyk EM, Middleton PF, Hague WM, Crowther CA. Women's views on postpartum testing for type 2 diabetes after gestational diabetes: Six month follow‐up to the DIAMIND randomised controlled trial. Primary Care Diabetes 2016;10(2):91‐102. [DOI: 10.1016/j.pcd.2015.07.003] - DOI - PubMed
Walkinshaw 2005
    1. Walkinshaw SA. Pregnancy in women with pre‐existing diabetes: management issues. Seminars in Fetal & Neonatal Medicine 2005;10:307‐15. - PubMed
Weintrob 1996
    1. Weintrob N, Karp M, Hod M. Short‐ and long‐ range complications in offspring of diabetic mothers. Journal of Diabetes and its Complications 1996;10:294‐301. - PubMed
WHO 1999
    1. World Health Organization. Report of a WHO consultation: definition, diagnosis and classification of diabetes mellitus. Geneva: WHO, 1999.
Yogev 2004
    1. Yogev Y, Langer O. The use of anti‐hyperglycaemic and hypoglycaemic agents in pregnancy. Fetal and Maternal Medicine Review 2004;15(2):133‐43.

References to other published versions of this review

Tieu 2010
    1. Tieu J, Coat S, Hague W, Middleton P. Oral anti‐diabetic agents for women with pre‐existing diabetes mellitus/impaired glucose tolerance or previous gestational diabetes mellitus. Cochrane Database of Systematic Reviews 2010, Issue 10. [DOI: 10.1002/14651858.CD007724.pub2] - DOI - PMC - PubMed

Publication types

MeSH terms