Skip to main content
Log in

Oral Hypoglycemic Agents in pregnancy: An Update

  • Review Article
  • Published:
The Journal of Obstetrics and Gynecology of India Aims and scope Submit manuscript

Abstract

Introduction

Traditionally, insulin has been the gold standard in the management of Type 2 diabetes in pregnancy and gestational diabetes. However, insulin therapy can be inconvenient because of the needs for multiple injections, its associated cost, pain at the injection site, need for refrigeration, and skillful handling of the syringes. This has led to the exploration of oral hypoglycemic agents as an alternative to insulin therapy.

Objectives

This review examines and evaluates the evidences on the efficacy, safety, and current recommendations of oral hypoglycemic agents.

Conclusion

The evidence of this study supports the use of glyburide and metformin in the management of Type 2 diabetes and gestational diabetes with no increased risk of neonatal hypoglycemia or congenital anomalies. The safety of these oral hypoglycemic agents are limited to the prenatal period and more randomized controlled trials are required to provide information on the long-term follow up on neonatal and cognitive development.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Jovanovic L, Pettitt DJ. Gestational diabetes mellitus. JAMA. 2001;286(20):2516–8.

    Article  PubMed  CAS  Google Scholar 

  2. Sheffield JS, Butler-Koster EL, Casey BM, et al. Maternal diabetes mellitus and infant malformations. Obstet Gynecol. 2002;100(5 pt 1):925–30.

    Article  PubMed  Google Scholar 

  3. Ferrara A, Kahn H, Quesenberry CP, et al. An increase in the incidence of gestational diabetes mellitus: Northern California. Obstet Gynecol. 2004;103:526–33.

    Article  PubMed  Google Scholar 

  4. Beischer NA, Oats J, Henry OA, et al. Incidence and severity of gestational diabetes mellitus according to country of birth in women living in Australia. Diabetes Care. 1991;40(Suppl. 2):35–8.

    Google Scholar 

  5. Langer O. Management of gestational diabetes. Clin Obstet Gynecol. 2000;43:106–15.

    Article  PubMed  CAS  Google Scholar 

  6. Schaefer-Graf UM, Buchanan TA, Xiang A, et al. Patterns of congenital anomalies and relationship to initial maternal fasting glucose levels in pregnancies complicated by type 2 and gestational diabetes. Am J Obstet Gynecol. 2000;182:313–20.

    Article  PubMed  CAS  Google Scholar 

  7. The HAPO Study Cooperative Research Group. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008;358(19):1991–2002.

    Article  Google Scholar 

  8. Lawlor DA, Lichtenstein P, Långström N. Association of maternal diabetes mellitus in pregnancy with offspring adiposity into early adulthood: sibling study in a prospective cohort of 280,866 men from 248,293 families. Circulation. 2011;123:258–65.

    Article  PubMed  Google Scholar 

  9. American College of Obstetricians and Gynecologists. Clinical management guidelines for obstetrician-gynecologists. ACOG Practice Bulletin. No 30. Obstet Gynecol. 2001;98:525–38.

    Google Scholar 

  10. American Diabetes Association. Standards of medical care in diabetes-2009. Diabetes Care. 2009;32(Suppl 1):S13–39.

    Article  Google Scholar 

  11. Reece EA, Homko C, Miodovnik M, et al. A consensus report of the diabetes in pregnancy study group of North America Conference, Little Rock, Arkansas, May 2002. J Matern Fetal Neonatal Med. 2002;12:362–4.

    Article  PubMed  CAS  Google Scholar 

  12. Langer O. Maternal glycemic criteria for insulin therapy in gestational diabetes mellitus. Diabetes Care. 1998;21(suppl 2):B91–8.

    PubMed  Google Scholar 

  13. Garcia-Bournissen F, Feig D, Koren G. Maternal-fetal transport of hypoglycaemic drug. Clin Pharmacokinet. 2003;42(4):303–13.

    Article  PubMed  CAS  Google Scholar 

  14. Sutherland H, Bewsher P, Cormack J, et al. Effect of moderate dosage of chlorpropamide in pregnancy on fetal outcome. Arch Dis Child. 1974;49(4):283–91.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  16. Groop L, Luzi L, Melander A,et al. Different effects of glyburide and glipizide on insulin secretion and hepatic glucose production in normal and NIDDM subjects. Diabetes. 1987;36(11):1320–8.

    Article  PubMed  CAS  Google Scholar 

  17. Groop LC, Barzilai N, Ratheiser K, et al. Dose-dependent effects of glyburide on insulin secretion and glucose uptake in humans. Diabetes Care. 1991;14(8):724–7.

    Article  PubMed  CAS  Google Scholar 

  18. Simonson DC, Farrannini E, Bevilacqua S, et al. Mechanism of improvement of glucose metabolism after chronic glyburide therapy. Diabetes Care. 1984;33:828–45.

    Google Scholar 

  19. Kemball ML, McIver C, Milner RD, et al. Neonatal hypoglycaemia in infants of diabetic mothers given sulphonylurea drugs in pregnancy. Arch Dis Child. 1970;45:696–701.

    Article  PubMed  CAS  Google Scholar 

  20. Elliot B, Langer O, Schenker S, et al. Insignificant transfer of glyburide occurs across the human placenta. Am J Obstet Gynecol. 1991;165:807–12.

    Article  Google Scholar 

  21. Elliot B, Schenker S, Langer O, et al. Comparative placental transport of oral hypoglycemic agents. A model of human placental drug transfer. Am J Obstet Gynecol. 1994;171:653–60.

    Article  Google Scholar 

  22. Elliot B, Langer O, Schussling F. A model of human placental drug transfer. Am J Obstet Gynecol. 1997;176:527–30.

    Article  Google Scholar 

  23. Koren G. Glyburide and fetal safety: transplacental pharmacokinetic considerations. Reprod Toxicol. 2001;15:225–9.

    Article  Google Scholar 

  24. Kraemer J, Klein J, Lubetsky A, et al. Perfusion studies of glyburide transfer across the human placenta: Implications for fetal safety. Am J Obstet Gynecol. 2006;195:270–4.

    Article  PubMed  CAS  Google Scholar 

  25. Langer O, editor. The diabetes in pregnancy dilemma: leading changes with simple solutions. New York: University Press of America; 2006.

    Google Scholar 

  26. Bailey CJ, Day C. Antidiabetic drugs. Br J Cardiol. 2003;10:128–13628.

    Google Scholar 

  27. DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med. 1999;131(4):281–303.

    Article  PubMed  CAS  Google Scholar 

  28. Langer O. Oral anti-hyperglycemic agents for the management of gestational diabetes mellitus. Obstet Gynecol Clin North Am. 2007;34(2):255–74.

    Article  PubMed  Google Scholar 

  29. Bailey C. Metformin—an update. Gen Pharmacol. 1993;24:1299–309.

    Article  PubMed  CAS  Google Scholar 

  30. Sirtori CR, Pasik C. Re-evaluation of a biguanide, metformin: mechanism of action and tolerability. Pharmacol Res. 1994;30:187–228.

    Article  PubMed  CAS  Google Scholar 

  31. Langer O. When diet fails: insulin and oral hypoglycemic agents as alternatives for the management of gestational diabetes mellitus. J Matern Fetal Neonatal Med. 2002;11:218–25.

    Article  PubMed  CAS  Google Scholar 

  32. Kirpichnikov D, McFarlane SI, Sowers JR. Metformin: an update. Ann Intern Med. 2002;137(1):25–33.

    Article  PubMed  CAS  Google Scholar 

  33. Hale TW, Kristensen JH, Hackett LP, et al. Transfer of metformin into human milk. Diabetologia. 2002;45(11):1509–14.

    Article  PubMed  CAS  Google Scholar 

  34. Gardiner SJ, Kirkpatrick CM, Begg EJ, et al. Transfer of metformin into human milk. Clin Pharmacol Ther. 2003;73(1):71–7.

    Article  PubMed  CAS  Google Scholar 

  35. Sevillano J, López-Pérez IC, Herrera E, et al. Englitazone administration to late pregnant rats produces delayed body growth and insulin resistance on their fetuses and neonates. Biochem J. 2005;389(3):913–8.

    Article  PubMed  CAS  Google Scholar 

  36. Chan LY, Yeung JH, Lau TK. Placental transfer of rosiglitazone in the first trimester of human pregnancy. Fertil Steril. 2005;83(4):955–8.

    Article  PubMed  CAS  Google Scholar 

  37. Stumvoll M. Thiazolidinedines—some recent development. Expert Opin Investig Drugs. 2003;12:1179–87.

    Article  PubMed  CAS  Google Scholar 

  38. Krentz AJ, Bailey CJ, Melander A. Thiazolidinediones for type 2 diabetes. BMJ. 2000;321:252–3.

    Article  PubMed  CAS  Google Scholar 

  39. Buchanan TA, Xiang AH, Peters RK, et al. Preservation of pancreatic beta-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high risk Hispanic women. Diabetes. 2002;51:2796–803.

    Article  PubMed  CAS  Google Scholar 

  40. Cataldo NA, Abbasi F, McLaughlin TL, et al. Improvement in insulin sensitivity followed by ovulation and pregnancy in a woman with polycystic ovary syndrome who was treated with rosiglitazone. Fertil Steril. 2001;76:1057–9.

    Article  PubMed  CAS  Google Scholar 

  41. Lebovitz HE. Alpha-glucosidase inhibitors. Source Department of Endocrinology, Metabolism, and Diabetes, State University of New York, Health Science Center at Brooklyn, New York, USA. Endocrinol Metab Clin North Am. 1997;26(3):539–551.

  42. Bertini AM, Silva JC, Taborda W, et al. Perinatal outcomes and the use of oral hypoglycemic agents. J Perinat Med. 2005;33:519.

    Article  PubMed  CAS  Google Scholar 

  43. Anjalakshi C, Balaji V, Balaji MS, et al. A prospective study comparing insulin and glibenclamide in gestational diabetes mellitus in Asian Indian women. Diabetes Res Clin Pract. 2007;76:474–5.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  45. Kremer CJ, Duff P. Glyburide for the treatment of gestational diabetes. Am J Obstet Gynecol. 2004;190(5):1438–9.

    Article  PubMed  CAS  Google Scholar 

  46. Ogunyemi D, Jesse M, Davidson M. Comparison of glyburide versus insulin in management of gestational diabetes mellitus. Endocr Pract. 2007;13:427–8.

    Article  PubMed  Google Scholar 

  47. Kahn BF, Davies JK, Lynch AM, et al. Predictors of glyburide failure in the treatment of gestational diabetes. Obstet Gynecol. 2006;107(6):1303–9.

    Article  PubMed  CAS  Google Scholar 

  48. Bertini AM, Silva J, Taborda W, et al. Perinatal outcomes and the use of oral hypoglycemic agents. J Perinat Med. 2005;33(15):519–23.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  50. Rowan JA, Hague WM, Gao W, et al. MiG Trial Investigators. Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med. 2008;358(19):2003–15.

    Article  PubMed  CAS  Google Scholar 

  51. Rowan JA, Rush EC, Obolonkin V, 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.

    Article  PubMed  CAS  Google Scholar 

  52. Jakubowicz DJ, Iuorno MJ, Jakubowicz S, et al. Effects of metformin on early pregnancy loss in the polycystic ovary syndrome. J Clin Endocrinol Metab. 2002;87:524–9.

    Article  PubMed  CAS  Google Scholar 

  53. Glueck CJ, Phillips H, Cameron D, et al. Continuing metformin throughout pregnancy in women with polycystic ovarian syndrome appears to safely reduce first trimester spontaneous abortions: a pilot study. Fertil Steril. 2001;75:46–52.

    Article  PubMed  CAS  Google Scholar 

  54. Glueck CJ, Wang P, Goldenberg N, et al. Pregnancy outcomes among women with polycystic ovarian syndrome treated with metformin. Hum Reprod. 2002;17:2858–64.

    Article  PubMed  CAS  Google Scholar 

  55. Glueck CJ, Ping W, Suichi K, et al. Metformin therapy throughout pregnancy reduces the development of gestational diabetes in women with polycystic ovarian syndrome. Fertil Steril. 2002;77:520–5.

    Article  PubMed  CAS  Google Scholar 

  56. Coetzee EJ, Ekpebach C, Levitt NS. Combined use of metformin and glibenclamide in gestational and type 2 diabetics. Program and abstract presented at the 4th International Symposium on Diabetes and Pregnancy, 29–31 March 2007 at the Hilton Istanbul hotel, Istanbul, Turkey.

  57. Hale TW, Kristensen JH, Hackett LP, et al. Transfer of metformin into human milk. Diabetologia. 2002;45:1509–14.

    Article  PubMed  CAS  Google Scholar 

  58. Akincia B, Tosunb P, Bekcib E, et al. Management of gestational diabetes by physicians in Turkey. Prim Care Diabetes. 2010;4:173–80.

    Article  Google Scholar 

  59. Arbit E, Kidron M. Oral insulin: the rationale for this approach and current developments. J Diabetes Sci Technol. 2009;3(3):562–7.

    PubMed  Google Scholar 

  60. Iyer H, Khedkar AP, Suryanarayan S, et al. An open label, two period, placebo controlled, multiple dose study to evaluate the effect of food on pharmacokinetic and pharmacodynamic of IN-105 10 mg in type 2 diabetes mellitus patients. Rome: European Association Study of Diabetes; 2008.

  61. Kidron M, Dinh S, Menachem Y, Abbas R, Variano B, Goldberg M, Arbit E, Bar-On H. A novel per-oral insulin formulation: proof of concept study in non-diabetic subjects. Diabet Med. 2004;21(4):354–7.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nagandla Kavitha.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kavitha, N., De, S. & Kanagasabai, S. Oral Hypoglycemic Agents in pregnancy: An Update. J Obstet Gynecol India 63, 82–87 (2013). https://doi.org/10.1007/s13224-012-0312-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13224-012-0312-z

Keywords

Navigation