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Using Oral Agents to Manage Gestational Diabetes: What Have We Learned?

  • Diabetes and Pregnancy (CJ Homko, Section Editor)
  • Published:
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Abstract

Insulin has been the mainstay of treatment of diabetes during pregnancy for decades. Although glyburide and metformin are classified as category B during pregnancy, recent research has suggested that these oral agents alone or in conjunction with insulin may be safe for the treatment of gestational diabetes (GDM). This paper summarizes the data on the use of glyburide and metformin for treatment of GDM.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 6/29/2014; Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/017498s031lbl.pdf.

  2. 7/5/2014; Available from: http://packageinserts.bms.com/pi/pi_glucophage_xr.pdf.

  3. Langer O et al. A comparison of glyburide and insulin in women with gestational diabetes mellitus. N Engl J Med. 2000;343(16):1134–8.

    Article  CAS  PubMed  Google Scholar 

  4. Camelo Castillo W et al. Trends in glyburide compared with insulin use for gestational diabetes treatment in the United States, 2000–2011. Obstet Gynecol. 2014;123(6):1177–84. doi:10.1097/AOG.0000000000000285.

    Article  CAS  PubMed  Google Scholar 

  5. Ogunyemi DA et al. Attitudes and practices of healthcare providers regarding gestational diabetes: results of a survey conducted at the 2010 meeting of the International Association of Diabetes in Pregnancy Study Group (IADPSG). Diabet Med. 2011;28(8):976–86.

    Article  CAS  PubMed  Google Scholar 

  6. Tattersall R. Diabetes: the biography. Oxford: Oxford University Press; 2009.

    Google Scholar 

  7. Jackson WP, Campbell GD. Chlorpropamide and perinatal mortality. Br Med J. 1963;2(5373):1652.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Malins JM et al. Sulphonylurea drugs in pregnancy. Br Med J. 1964;2(5402):187.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Douglas CP, Richards R. Use of chlorpropamide in the treatment of diabetes in pregnancy. Diabetes. 1967;16(1):60–1.

    Article  CAS  PubMed  Google Scholar 

  10. Notelovitz M. Sulphonylurea therapy in the treatment of the pregnant diabetic. S Afr Med J. 1971;45(9):226–9.

    CAS  PubMed  Google Scholar 

  11. Sutherland HW et al. Effect of moderate dosage of chlorpropamide in pregnancy on fetal outcome. Arch Dis Child. 1974;49(4):283–91.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Sutherland HW et al. Evaluation of chlorpropamide in chemical diabetes diagnosed during pregnancy. Br Med J. 1973;3(5870):9–13.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Kemball ML et al. Neonatal hypoglycaemia in infants of diabetic mothers given sulphonylurea drugs in pregnancy. Arch Dis Child. 1970;45(243):696–701.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Zucker P, Simon G. Prolonged symptomatic neonatal hypoglycemia associated with maternal chlorpropamide therapy. Pediatrics. 1968;42(5):824–5.

    CAS  PubMed  Google Scholar 

  15. Uhrig JD, Hurley RM. Chlorpropamide in pregnancy and transient neonatal diabetes insipidus. Can Med Assoc J. 1983;128(4):368. 370–1.

    PubMed Central  CAS  PubMed  Google Scholar 

  16. Christesen H, Melander A. Prolonged elimination of tolbutamide in a premature newborn with hyperinsulinaemic hypoglycaemia. Eur J Endocrinol. 1998;138(6):698–701.

    Article  CAS  PubMed  Google Scholar 

  17. 7/5/14; Available from: http://en.wikipedia.org/wiki/Metformin#History.

  18. Ramos GA et al. Comparison of glyburide and insulin for the management of gestational diabetics with markedly elevated oral glucose challenge test and fasting hyperglycemia. J Perinatol. 2007;27(5):262–7.

    Article  CAS  PubMed  Google Scholar 

  19. Coetzee EJ, Jackson WPU. The management of non-insulin-dependent diabetes during pregnancy. Diabetes Res Clin Pract. 1985;1(5):281–7.

    Article  PubMed  Google Scholar 

  20. Hellmuth E, Damm P, Molsted-Pedersen L. Oral hypoglycaemic agents in 118 diabetic pregnancies. Diabet Med. 2000;17(7):507–11.

    Article  CAS  PubMed  Google Scholar 

  21. Elliott BD et al. Insignificant transfer of glyburide occurs across the human placenta. Am J Obstet Gynecol. 1991;165(4 Pt 1):807–12.

    Article  CAS  PubMed  Google Scholar 

  22. Elliott BD et al. Comparative placental transport of oral hypoglycemic agents in humans: a model of human placental drug transfer. Am J Obstet Gynecol. 1994;171(3):653–60.

    Article  CAS  PubMed  Google Scholar 

  23. Gedeon C et al. Transport of glyburide by placental ABC transporters: implications in fetal drug exposure. Placenta. 2006;27(11–12):1096–102.

    Article  CAS  PubMed  Google Scholar 

  24. Nanovskaya TN et al. Effect of albumin on transplacental transfer and distribution of rosiglitazone and glyburide. J Matern Fetal Neonatal Med. 2008;21(3):197–207.

    Article  CAS  PubMed  Google Scholar 

  25. Koren G. Glyburide and fetal safety; transplacental pharmacokinetic considerations. Reprod Toxicol. 2001;15(3):227–9.

    Article  CAS  PubMed  Google Scholar 

  26. Zharikova OL et al. Identification of the major human hepatic and placental enzymes responsible for the biotransformation of glyburide. Biochem Pharmacol. 2009;78(12):1483–90.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Ke AB et al. Expansion of a PBPK model to predict disposition in pregnant women of drugs cleared via multiple CYP enzymes, including CYP2B6, CYP2C9 and CYP2C19. Br J Clin Pharmacol. 2014;77(3):554–70.

    Article  CAS  PubMed  Google Scholar 

  28. Kraemer J et al. Perfusion studies of glyburide transfer across the human placenta: implications for fetal safety. Am J Obstet Gynecol. 2006;195(1):270–4.

    Article  CAS  PubMed  Google Scholar 

  29. Pollex EK et al. Breast cancer resistance protein (BCRP)-mediated glyburide transport: effect of the C421A/Q141K BCRP single-nucleotide polymorphism. Drug Metab Dispos. 2010;38(5):740–4.

    Article  CAS  PubMed  Google Scholar 

  30. Hemauer SJ et al. Role of human placental apical membrane transporters in the efflux of glyburide, rosiglitazone, and metformin. Am J Obstet Gynecol. 2010;202(4):383.e1–7.

    Google Scholar 

  31. Iqbal M et al. Placental drug transporters and their role in fetal protection. Placenta. 2012;33(3):137–42.

    Article  CAS  PubMed  Google Scholar 

  32. Hebert MF et al. Are we optimizing gestational diabetes treatment with glyburide? The pharmacologic basis for better clinical practice. Clin Pharmacol Ther. 2009;85(6):607–14.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Lim JM et al. A comparison between the pregnancy outcome of women with gestation diabetes treated with glibenclamide and those treated with insulin. Med J Malays. 1997;52(4):377–81.

    CAS  Google Scholar 

  34. Goetzl L, Wilkins I. Glyburide compared to insulin for the treatment of gestational diabetes mellitus: a cost analysis. J Perinatol. 2002;22(5):403–6.

    Article  PubMed  Google Scholar 

  35. Jacobson GF et al. Comparison of glyburide and insulin for the management of gestational diabetes in a large managed care organization. Am J Obstet Gynecol. 2005;193(1):118–24.

    Article  CAS  PubMed  Google Scholar 

  36. Rochon M et al. Glyburide for the management of gestational diabetes: risk factors predictive of failure and associated pregnancy outcomes. Am J Obstet Gynecol. 2006;195(4):1090–4.

    Article  CAS  PubMed  Google Scholar 

  37. Holt RIG et al. The effectiveness of glibenclamide in women with gestational diabetes. Diabetes Obes Metab. 2008;10(10):906–11.

    Article  CAS  PubMed  Google Scholar 

  38. Mathews JE et al. Retrospective cohort study comparing neonatal outcomes of women treated with glyburide or insulin in gestational diabetes: a 5-year experience in a South Indian teaching hospital. Indian J Med Sci. 2011;65(11):476–81.

    Article  PubMed  Google Scholar 

  39. Yogev Y et al. Glyburide in gestational diabetes—prediction of treatment failure. J Matern Fetal Neonatal Med. 2011;24(6):842–6.

    Article  CAS  PubMed  Google Scholar 

  40. Chmait R, Dinise T, Moore T. Prospective observational study to establish predictors of glyburide success in women with gestational diabetes mellitus. J Perinatol. 2004;24(10):617–22.

    Article  CAS  PubMed  Google Scholar 

  41. Bertini Anna, M., et al., Perinatal outcomes and the use of oral hypoglycemic agents, in Journal of Perinatal Medicine. 2005. p. 519.

  42. Cheng YW et al. Treatment of gestational diabetes mellitus: glyburide compared to subcutaneous insulin therapy and associated perinatal outcomes. J Matern Fetal Neonatal Med. 2012;25(4):379–84. This is a large retrospective study of glyburide use in GDM. It is useful as it illustrates the outcomes of the real life application of glyburide in GDM.

  43. Langer O et al. Insulin and glyburide therapy: dosage, severity level of gestational diabetes, and pregnancy outcome. Am J Obstet Gynecol. 2005;192(1):134–9.

    Article  CAS  PubMed  Google Scholar 

  44. Lain KY et al. Neonatal adiposity following maternal treatment of gestational diabetes with glyburide compared with insulin. Am J Obstet Gynecol. 2009;200(5):501.e1–6.

    Google Scholar 

  45. Tempe A, Mayanglambam RD. Glyburide as treatment option for gestational diabetes mellitus. J Obstet Gynaecol Res. 2013;39(6):1147–52.

    Article  PubMed  Google Scholar 

  46. Anjalakshi C et al. A prospective study comparing insulin and glibenclamide in gestational diabetes mellitus in Asian Indian women. Diabetes Res Clin Pract. 2007;76(3):474–5.

    Article  CAS  PubMed  Google Scholar 

  47. Zeng Y-c et al. The use of glyburide in the management of gestational diabetes mellitus: a meta-analysis. Adv Med Sci. 2014;59(1):95–101. This is a meta-analysis of RCTs of glyburide versus insulin. Most RCTs on this topic are under-powered to detect differences in neonatal outcomes, hence, the importance of a meta-analysis of the topic.

  48. Wareing M et al. Glibenclamide inhibits agonist-induced vasoconstriction of placental chorionic plate arteries. Placenta. 2006;27(6–7):660–8.

    Article  CAS  PubMed  Google Scholar 

  49. Petty RG, Pearson JD. The influence of hypoglycaemic agents on the growth and metabolism of human endothelial cells. Diabet Med. 1992;9(1):30–7.

    Article  CAS  PubMed  Google Scholar 

  50. Downing SJ, Hollingsworth M. Antagonism of relaxin by glibenclamide in the uterus of the rat in vivo. Br J Pharmacol. 1991;104(1):71–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Ballas J, Moore TR, Ramos GA. Management of diabetes in pregnancy. Curr Diabetes Rep. 2012;12(1):33–42.

    Article  CAS  Google Scholar 

  52. Nicholson W, Baptiste-Roberts K. Oral hypoglycaemic agents during pregnancy: the evidence for effectiveness and safety. Best Prac Res Clin Obstet Gynaecol. 2011;25(1):51–63.

    Article  Google Scholar 

  53. Cassina, M., et al., First-trimester exposure to metformin and risk of birth defects: a systematic review and meta-analysis. Human Reproduction Update, 2014.

  54. Rowan JA, Mi GI. A trial in progress: gestational diabetes. Treatment with metformin compared with insulin (the Metformin in Gestational Diabetes [MiG] trial). Diabetes Care. 2007;30 Suppl 2:S214–9.

    Article  CAS  PubMed  Google Scholar 

  55. Rowan JA et al. Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med. 2008;358(19):2003–15.

    Article  CAS  PubMed  Google Scholar 

  56. Feig DS. Metformin therapy for gestational diabetes mellitus: are we there yet? Nat Clin Pract Endocrinol Metab. 2008;4(12):654–5.

    Article  CAS  PubMed  Google Scholar 

  57. Rowan JA et al. Glycemia and its relationship to outcomes in the metformin in gestational diabetes trial. Diabetes Care. 2010;33(1):9–16.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Rowan JA et al. Metformin in gestational diabetes: the offspring follow-up (MiG TOFU): body composition at 2 years of age. Diabetes Care. 2011;34(10):2279–84. This is the most recent paper in a very important series by these authors reporting on the use of metformin in GDM and the long-term outcomes on offspring.

  59. Goh JE, Sadler L, Rowan J. Metformin for gestational diabetes in routine clinical practice. Diabet Med. 2011;28(9):1082–7.

    Article  CAS  PubMed  Google Scholar 

  60. Hickman MA et al. Metformin compared with insulin in the treatment of pregnant women with overt diabetes: a randomized controlled trial. Am J Perinatol. 2013;30(6):483–90.

    Article  PubMed  Google Scholar 

  61. Ekpebegh CO et al. A 10-year retrospective analysis of pregnancy outcome in pregestational type 2 diabetes: comparison of insulin and oral glucose-lowering agents. Diabet Med. 2007;24(3):253–8.

    Article  CAS  PubMed  Google Scholar 

  62. Tertti K et al. Comparison of metformin and insulin in the treatment of gestational diabetes: a retrospective, case-control study. Rev Diabet Stud. 2008;5(2):95–101.

    Article  PubMed Central  PubMed  Google Scholar 

  63. Gandhi P et al. Introduction of metformin for gestational diabetes mellitus in clinical practice: has it had an impact? Eur J Obstet Gynecol Reprod Biol. 2012;160(2):147–50.

    Article  CAS  PubMed  Google Scholar 

  64. Balani J et al. Pregnancy outcomes in women with gestational diabetes treated with metformin or insulin: a case-control study. Diabet Med. 2009;26(8):798–802.

    Article  CAS  PubMed  Google Scholar 

  65. Mesdaghinia E et al. Comparison of newborn outcomes in women with gestational diabetes mellitus treated with metformin or insulin: a randomised blinded trial. Int J Prev Med. 2013;4(3):327–33.

    PubMed Central  PubMed  Google Scholar 

  66. Moore LE et al. Metformin compared with glyburide in gestational diabetes: a randomized controlled trial. Obstet Gynecol. 2010;115(1):55–9.

    Article  CAS  PubMed  Google Scholar 

  67. Silva JC et al. Metformin compared with glyburide for the management of gestational diabetes. Int J Gynecol Obstet. 2010;111(1):37–40.

    Article  CAS  Google Scholar 

  68. Zarate A et al. Effectiveness of acarbose in the control of glucose tolerance worsening in pregnancy. Ginecol Obstet Mex. 2000;68:42–5.

    CAS  PubMed  Google Scholar 

  69. Wilton LV et al. The outcomes of pregnancy in women exposed to newly marketed drugs in general practice in England. Br J Obstet Gynaecol. 1998;105(8):882–9.

    Article  CAS  PubMed  Google Scholar 

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Conflict of Interest

Elizabeth Buschur, Florence Brown, and Jennifer Wyckoff declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. University of Michigan, 24 Frank Lloyd Wright Drive, Ann Arbor, MI, 48105, USA

    Elizabeth Buschur & Jennifer Wyckoff

  2. Joslin Diabetes Center, 1 Joslin Place, Boston, MA, 02215, USA

    Florence Brown

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  1. Elizabeth Buschur
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  2. Florence Brown
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  3. Jennifer Wyckoff
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Correspondence to Jennifer Wyckoff.

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This article is part of the Topical Collection on Diabetes and Pregnancy

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Buschur, E., Brown, F. & Wyckoff, J. Using Oral Agents to Manage Gestational Diabetes: What Have We Learned?. Curr Diab Rep 15, 4 (2015). https://doi.org/10.1007/s11892-014-0570-5

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  • DOI: https://doi.org/10.1007/s11892-014-0570-5

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