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Meta-Analysis
. 2009 Jul 8;2009(3):CD003395.
doi: 10.1002/14651858.CD003395.pub2.

Treatments for gestational diabetes

Nisreen Alwan  1 , Derek J Tuffnell, Jane West
Affiliations
Meta-Analysis

Treatments for gestational diabetes

Nisreen Alwan et al. Cochrane Database Syst Rev. .

Abstract

Background: Gestational diabetes (GDM) affects 3% to 6% of all pregnancies. Women are often intensively managed with increased obstetric monitoring, dietary regulation, and insulin. However, there has been no sound evidence base to support intensive treatment. The key issue for clinicians and consumers is whether treatment of GDM improves perinatal outcome.

Objectives: To compare the effect of alternative treatment policies for GDM on both maternal and infant outcomes.

Search strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (January 2009) and bibliographies of relevant papers.

Selection criteria: Randomised controlled trials comparing alternative management strategies for women with GDM and impaired glucose tolerance in pregnancy.

Data collection and analysis: Two authors and a member of the Cochrane Pregnancy and Childbirth Group's editorial team extracted and checked data independently. Disagreements were resolved through discussion with the third author.

Main results: Eight randomised controlled trials (1418 women) were included.Caesarean section rate was not significantly different when comparing any specific treatment with routine antenatal care (ANC) including data from five trials with 1255 participants (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.80 to 1.12). However, when comparing oral hypoglycaemics with insulin as treatment for GDM, there was a significant reduction (RR 0.46, 95% CI 0.27 to 0.77, two trials, 90 participants). There was a reduction in the risk of pre-eclampsia with intensive treatment (including dietary advice and insulin) compared to routine ANC (RR 0.65, 95% CI 0.48 to 0.88, one trial, 1000 participants). More women had their labours induced when given specific treatment compared to routine ANC (RR 1.33, 95% CI 1.13 to 1.57, two trials, 1068 participants). The composite outcome of perinatal morbidity (death, shoulder dystocia, bone fracture and nerve palsy) was significantly reduced for those receiving intensive treatment for mild GDM compared to routine ANC (RR 0.32, 95% CI 0.14 to 0.73, one trial, 1030 infants).There was a reduction in the proportion of infants weighing more than 4000 grams (RR 0.46, 95% CI 0.34 to 0.63, one trial, 1030 infants) and the proportion of infants weighing greater than the 90th birth centile (RR 0.55, 95% CI 0.30 to 0.99, three trials, 223 infants) of mothers receiving specific treatment for GDM compared to routine ANC. However, there was no statistically significant difference in this proportion between infants of mothers receiving oral drugs compared to insulin as treatment for GDM.

Authors' conclusions: Specific treatment including dietary advice and insulin for mild GDM reduces the risk of maternal and perinatal morbidity. However, it is associated with higher risk of labour induction. More research is needed to assess the impact of different types of intensive treatment, including oral drugs and insulin, on individual short- and long-term infant outcomes.

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Conflict of interest statement

None known.

Figures

1.1
1.1. Analysis
Comparison 1 Any specific treatment versus routine antenatal care (subgroups by type of specific treatment), Outcome 1 Antenatal hospital visits.
1.2
1.2. Analysis
Comparison 1 Any specific treatment versus routine antenatal care (subgroups by type of specific treatment), Outcome 2 Antenatal hospital admissions.
1.3
1.3. Analysis
Comparison 1 Any specific treatment versus routine antenatal care (subgroups by type of specific treatment), Outcome 3 Number of extra blood tests.
1.4
1.4. Analysis
Comparison 1 Any specific treatment versus routine antenatal care (subgroups by type of specific treatment), Outcome 4 Pre‐eclampsia.
1.5
1.5. Analysis
Comparison 1 Any specific treatment versus routine antenatal care (subgroups by type of specific treatment), Outcome 5 Need for insulin treatment.
1.6
1.6. Analysis
Comparison 1 Any specific treatment versus routine antenatal care (subgroups by type of specific treatment), Outcome 6 Induction of labour.
1.7
1.7. Analysis
Comparison 1 Any specific treatment versus routine antenatal care (subgroups by type of specific treatment), Outcome 7 Operative vaginal delivery.
1.8
1.8. Analysis
Comparison 1 Any specific treatment versus routine antenatal care (subgroups by type of specific treatment), Outcome 8 Caesarean section.
1.9
1.9. Analysis
Comparison 1 Any specific treatment versus routine antenatal care (subgroups by type of specific treatment), Outcome 9 Postpartum haemorrhage.
1.10
1.10. Analysis
Comparison 1 Any specific treatment versus routine antenatal care (subgroups by type of specific treatment), Outcome 10 Gestational age at delivery.
1.11
1.11. Analysis
Comparison 1 Any specific treatment versus routine antenatal care (subgroups by type of specific treatment), Outcome 11 Birthweight > 4000 g.
1.12
1.12. Analysis
Comparison 1 Any specific treatment versus routine antenatal care (subgroups by type of specific treatment), Outcome 12 Birthweight > 90th centile.
1.13
1.13. Analysis
Comparison 1 Any specific treatment versus routine antenatal care (subgroups by type of specific treatment), Outcome 13 Perinatal death.
1.14
1.14. Analysis
Comparison 1 Any specific treatment versus routine antenatal care (subgroups by type of specific treatment), Outcome 14 Bone fracture in infant.
1.15
1.15. Analysis
Comparison 1 Any specific treatment versus routine antenatal care (subgroups by type of specific treatment), Outcome 15 Nerve palsy in infant.
1.16
1.16. Analysis
Comparison 1 Any specific treatment versus routine antenatal care (subgroups by type of specific treatment), Outcome 16 Shoulder dystocia.
1.17
1.17. Analysis
Comparison 1 Any specific treatment versus routine antenatal care (subgroups by type of specific treatment), Outcome 17 Composite outcome in infant (death, shoulder dystocia, nerve palsy, bone fracture).
1.18
1.18. Analysis
Comparison 1 Any specific treatment versus routine antenatal care (subgroups by type of specific treatment), Outcome 18 Admission to neonatal care/special baby care unit.
1.19
1.19. Analysis
Comparison 1 Any specific treatment versus routine antenatal care (subgroups by type of specific treatment), Outcome 19 Respiratory disress syndrome/need for ventilation in infant.
1.20
1.20. Analysis
Comparison 1 Any specific treatment versus routine antenatal care (subgroups by type of specific treatment), Outcome 20 Neonatal hypoglycemia.
1.21
1.21. Analysis
Comparison 1 Any specific treatment versus routine antenatal care (subgroups by type of specific treatment), Outcome 21 Length of hospital stay (days).
2.1
2.1. Analysis
Comparison 2 Oral hypoglycemic drugs versus insulin therapy, Outcome 1 Caesarean section.
2.2
2.2. Analysis
Comparison 2 Oral hypoglycemic drugs versus insulin therapy, Outcome 2 Operative vaginal delivery.
2.3
2.3. Analysis
Comparison 2 Oral hypoglycemic drugs versus insulin therapy, Outcome 3 Induction of labour.
2.4
2.4. Analysis
Comparison 2 Oral hypoglycemic drugs versus insulin therapy, Outcome 4 Postpartum haemorrhage.
2.5
2.5. Analysis
Comparison 2 Oral hypoglycemic drugs versus insulin therapy, Outcome 5 Gestational age at delivery.
2.6
2.6. Analysis
Comparison 2 Oral hypoglycemic drugs versus insulin therapy, Outcome 6 Birthweight > 4000 g.
2.7
2.7. Analysis
Comparison 2 Oral hypoglycemic drugs versus insulin therapy, Outcome 7 Birthweight > 90th centile.
2.8
2.8. Analysis
Comparison 2 Oral hypoglycemic drugs versus insulin therapy, Outcome 8 Birthweight (g).
2.9
2.9. Analysis
Comparison 2 Oral hypoglycemic drugs versus insulin therapy, Outcome 9 Neonatal hypoglycemia.
2.10
2.10. Analysis
Comparison 2 Oral hypoglycemic drugs versus insulin therapy, Outcome 10 Admission to neonatal care/special baby care unit.
2.11
2.11. Analysis
Comparison 2 Oral hypoglycemic drugs versus insulin therapy, Outcome 11 Shoulder dystocia.
2.12
2.12. Analysis
Comparison 2 Oral hypoglycemic drugs versus insulin therapy, Outcome 12 Respiratory disress syndrome/need for ventilation in infant.
3.1
3.1. Analysis
Comparison 3 Acarbose versus insulin therapy, Outcome 1 Gestational age at delivery.
3.2
3.2. Analysis
Comparison 3 Acarbose versus insulin therapy, Outcome 2 Birthweight (g).
3.3
3.3. Analysis
Comparison 3 Acarbose versus insulin therapy, Outcome 3 Birthweight > 90th centile.
3.4
3.4. Analysis
Comparison 3 Acarbose versus insulin therapy, Outcome 4 Neonatal hypoglycemia.
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    1. Snyder J, Morin L, Meltzer S, Nadeau J. Gestational diabetes and glycemic control: a randomized clinical trial. American Journal of Obstetrics and Gynecology 1998;178(1 Pt 2):55.
Thompson 1990 {published data only}
    1. Thompson DJ, Porter KB, Gunnells DJ, Wagner PC, Spinnato JA. Prophylactic insulin in the management of gestational diabetes. Obstetrics & Gynecology 1990;75:960‐4. - PubMed
Todorova 2007 {published data only}
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Yang 2003 {published and unpublished data}
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References to studies awaiting assessment

Balaji 2010 {published data only}
    1. Balaji V, Balaji MS, Alexander C, Ashalata S, Sheela R, Suresh S, et al. Premixed insulin aspart 30 (Biasp 30) vs. premixed human insulin 30 (BHI 30) in gestational diabetes mellitus‐‐a pilot study. Journal of the Association of Physicians of India 2010;58:99‐101. - PubMed
Bertini 2009 {published data only}
    1. Bertini AM. Up to date treatment of gestational diabetes mellitus. Journal of Perinatal Medicine 2009;37(Suppl 1):3.
Cortez 2006 {published data only}
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Durnwald 2011 {published data only}
    1. Durnwald CP, Mele L, Spong CY, Ramin SM, Varner MW, Rouse DJ, et al. Glycemic characteristics and neonatal outcomes of women treated for mild gestational diabetes. Obstetrics & Gynecology 2011;117(4):819‐27. - PMC - PubMed
Elnour 2008 {published data only}
    1. Elnour AA, Mugammar IT, Jaber T, Revel T, McElnay JC. Pharmaceutical care of patients with gestational diabetes mellitus. Journal of Evaluation in Clinical Practice 2008;14(1):131‐40. - PubMed
Ferrara 2008 {published data only}
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Garcia‐Patterson 2001 {published data only}
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Gillman 2010 {published data only}
    1. Gillman MW, Oakey H, Baghurst PA, Volkmer RE, Robinson JS, Crowther CA. Effect of treatment of gestational diabetes mellitus on obesity in the next generation. Diabetes Care 2010;33(5):964‐8. - PMC - PubMed
Grant 2011 {published data only}
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Hickman 2011 {published data only}
    1. Hickman A. Effectiveness of metformin compared to insulin in pregnant women with mild preexisting or early gestational diabetes (MIPOD). ClinicalTrials.gov (http://clinicaltrials.gov/) (accessed 15 February 2011) 2011.
Hutchinson 2008 {published data only}
    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.
Ijas 2011 {published data only}
    1. Ijas H, Vaarasmaki M, Morin‐Papunen L, Keravuo R, Ebeling T, Saarela T, et al. Metformin should be considered in the treatment of gestational diabetes: a prospective randomised study. BJOG: an international journal of obstetrics and gynaecology 2011;118(7):880‐5. - PubMed
Keely 2008 {published data only}
    1. Keely EJ, Malcolm JC, Hadjiyannakis S, Gaboury I, Lough G, Lawson ML. Prevalence of metabolic markers of insulin resistance in offspring of gestational diabetes pregnancies. Pediatric Diabetes 2008;9(1):53‐9. - PubMed
Lain 2008 {published data only}
    1. Lain K, Garabedian M, Daftary A, Jeyabalan A. Maternal and neonatal metabolic biomarkers in gestational diabetes treated with glyburide compared to insulin. American Journal of Obstetrics and Gynecology 2008;199(6 Suppl 1):S199. - PubMed
    1. Lain K, Garabedian M, Daftary A, Jeyabalan A. Neonatal adiposity following maternal treatment of gestational diabetes with glyburide compared to insulin. American Journal of Obstetrics and Gynecology 2008;199(6 Suppl 1):S34. - PubMed
Lain 2009 {published data only}
    1. Lain KY, Garabedian MJ, Daftary A, Jeyabalan A. Neonatal adiposity following maternal treatment of gestational diabetes with glyburide compared with insulin. American Journal of Obstetrics and Gynecology 2009;200(5):501.e1‐6. - PubMed
Landon 2009 {published data only}
    1. Landon MB, Spong CY, Thom 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
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.
Mendelson 2008 {published data only}
    1. Mendelson SG, McNeese‐Smith D, Koniak‐Griffin D, Nyamathi A, Lu MC. A community‐based parish nurse intervention program for Mexican American women with gestational diabetes. Journal of Obstetric, Gynecologic, and Neonatal Nursing 2008;37(4):415‐25. - PubMed
Moore 2008 {published data only}
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Moore 2010 {published data only}
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Moses 2009 {published data only}
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Ong 2009 {published data only}
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Refuerzo 2011 {published data only}
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Rowan 2008 {published data only}
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Rowan 2010 {published data only}
    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
Silva 2007 {published data only}
    1. Silva JC, Bertini AM, Taborda W, Becker F, Bebber FR, Aquim GM, et al. Glibenclamide in the treatment for gestational diabetes mellitus in a compared study to insulin. Arquivos Brasileiros de Endocrinologia e Metabologia 2007;51(4):541‐6. - PubMed
Silva 2010 {published data only}
    1. Silva JC, Pacheco C, Bizato J, Souza BV, Ribeiro TE, Bertini AM. Metformin compared with glyburide for the management of gestational diabetes. International Journal of Gynecology & Obstetrics 2010;111(1):37‐40. - PubMed
Zanganeh 2010 {published data only}
    1. Zanganeh M. The comparative study of therapeutic effects of insulin and glibenclamide in the gestational diabetes mellitus. IRCT Iranian Registry of Clinical Trials (www.irct.ir) (accessed 6 December 2010).

References to ongoing studies

Crowther 2007 {published data only}
    1. Crowther C. Dietary and lifestyle advice for women with borderline gestational glucose intolerance. Australian Clinical Trials Registry (www.actr.org.au) (accessed 21 June 2007).
Golladay 2006 {published data only}
    1. Golladay EC. Glyburide compared to insulin in the management of White's classification A2 gestational diabetes. ClinicalTrials.gov (http://clinicaltrials.gov/) (accessed 21 March 2006).
Kipikasa 2008 {published data only}
    1. Kipikasa JH. Comparison of glucovance to insulin for diabetes during pregnancy. ClinicalTrials.gov (http://clinicaltrials.gov/) (accessed 20 February 2008).
Landon 2002 {published and unpublished data}
    1. Landon MB. A prospective multicenter randomized treatment trial of mild gestational diabetes. American Journal of Obstetrics and Gynecology 2008;199(6 Suppl 1):S2.
    1. Landon MB, Thom E, Spong CY, Carpenter M, Mele L, Johnson F, Tillinghast J, Anderson G. The National Institute of Child Health and Human Development Maternal‐Fetal Medicine Unit Network randomised clinical trial in progress. Diabetes Care 2007;30:S194‐9. - PubMed
    1. Landon MB, Thom E, Spong CY, Gabbe SG, Leindecker S, Johnson F, et al. A planned randomized clinical trial of treatment for mild gestational diabetes mellitus. Journal of Maternal‐Fetal & Neonatal Medicine 2002;11(4):226‐31. - PubMed
Rowan 2005 {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. Australian Clinical Trials Register (http://www.actr.org/actr) (accessed 6 December 2005).

Additional references

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References to other published versions of this review

CDSR 2003
    1. Tuffnell DJ, West J, Walkinshaw SA. Treatments for gestational diabetes and impaired glucose tolerance in pregnancy. Cochrane Database of Systematic Reviews 2003, Issue 3. [Art. No.: CD003395. DOI: 10.1002/14651858.CD003395] - PubMed

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