Review of metformin and glyburide in the management of gestational diabetes

Main Article Content

Dana G. Carroll
Kristi W. Kelley


Diabetes, Gestational, Glyburide, Metformin, Insulin, Comparative Effectiveness Research, Patient Safety, Pregnancy


Background: Worldwide, gestational diabetes affects 15% of pregnancies. It is recommended in patients with gestational diabetes to initiate diet therapy and if this is not adequate, insulin is the next treatment modality. While insulin is the preferred drug therapy to manage gestational diabetes in the majority of women, it may not always be the best option for all women.

Objective: The purpose of this review is to assess the efficacy and safety of oral agents for treatment of gestational diabetes.

Methods: A literature search of the MEDLINE, Ovid databases and Google Scholar was performed using the search term “gestational diabetes” combined with each “metformin” and “glyburide”. The time frame for the search was inception through August 2014. Randomized controlled trials and cohort (both prospective and retrospective) trials, published in English, with human participants were included. Studies included only pregnant women diagnosed with gestational diabetes.

Results: There were no significant differences in preterm deliveries, delivery modes, macrosomia, and birth weights and large for gestational age when utilizing glyburide vs insulin for gestational diabetes management. There were significantly higher neonatal intensive care unit admissions as well as longer lengths of stay for hypoglycemia and respiratory distress in babies whose mothers were treated with glyburide versus insulin. For the studies comparing metformin to insulin, there are no significant differences reported for birth weight, gestational age, delivery mode, prematurity and perinatal deaths. Women taking metformin may require supplemental insulin more frequently than those taking glyburide.

Conclusion: Glyburide and metformin appear to be safe and effective to manage blood glucose in patients with gestational diabetes who prefer to not utilize insulin or who cannot afford insulin therapy. All other oral therapies to manage blood glucose levels during gestational diabetes should be reserved until additional evidence is available regarding safety and efficacy to both mother and fetus.

Abstract 2156 | PDF Downloads 1291 file Downloads 327


1. National Diabetes Statistics 2011. National Institutes of Health. Available at: (accessed June 26, 2013).

2. American Diabetes Association. Standards of medical care in Diabetes-2014. Diabetes Care. 2014;37(Suppl 1):S14-S80. doi: 10.2337/dc14-S014

3. Gestational Diabetes. Internal Diabetes Federation. (accessed September 22, 2014).

4. Committee on Practice Bulletins--Obstetrics.Practice Bulletin No. 137: Gestational diabetes mellitus. Obstet Gynecol. 2013;122(2 Pt 1):406-416. doi: 10.1097/01.AOG.0000433006.09219.f1

5. Pregnancy and Diabetes. International Diabetes Federation. (accessed September 22, 2014).

6. Diabetes and Pregnancy. Canadian Diabetes Association Clinical Practice Guidelines. (accessed September 22, 2014).

7. Diabetes in Pregnancy. National Institute for Health and Clinical Excellence. (accessed September 22, 2014).

8. Langer O, Conway DL, Berkus MD, Xenakis EM, Gonzales O. A comparison of glyburide and insulin in women with gestational diabetes. N Engl J Med. 2000;343(16):1134-1138.

9. 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):617-622.

10. Conway DL, Gonzales O, Skiver D. Use of glyburide for the treatment of gestational diabetes: the San Antonio experience. J Matern Fetal Neonatal Med. 2004;15(1):51-55.

11. Jacobson GF, Ramos GA, Ching JY, Kirby RS, Ferrara A, Field DR.Comparison of glyburide and insulin for the management of gestational diabetes in a large managed care organization. Am J Obstet Gynecol. 2005;193(1):118-124.

12. Rochon M, Rand L, Roth L, Gaddipati S. Glyburide for the management of gestational diabetes: risk factors predictive of failure and associated pregnancy outcomes. Am J Obstet Gynecol. 2006;195(4):1090-1094.

13. Kahn BF, Davies JK, Lynch AM, Reynolds RM, Barbour LA. Predictors of glyburide failure in the treatment of gestational diabetes. Obstet Gynecol. 2006;107(6):1303-1309.

14. Yogev Y, Melamed N, Chen R, Nassie D, Pardo J, Hod M. Glyburide in gestational diabetes--prediction of treatment failure. J Matern Fetal Neonatal Med. 2011;24(6):842-846. doi: 10.3109/14767058.2010.531323

15. Kremer CJ, Duff P. Glyburide for the treatment of gestational diabetes. Am J Obstet Gynecol. 2004;190(5):1438-1439.

16. Cheng YW, Chung JH, Block-Kurbisch I, Inturrisi M, Caughey AB. Treatment of gestational diabetes mellitus: glyburide compared to subcutaneous insulin therapy and associated perinatal outcomes. J Matern Fetal Neonatal Med. 2012;25(4):379-384. doi: 10.3109/14767058.2011.580402

17. Tempe A, Mayanglambam RD. Glyburide as treatment option for gestational diabetes mellitus. J Obstet Gynaecol Res. 2013;39(6):1147-1152. doi: 10.1111/jog.12042

18. Hellmuth E, Damm P, Mølsted-Pedersen L. Oral hypoglycaemic agents in 118 diabetic pregnancies. Diabet Med. 2000;17(7):507-511.

19. Moore LE, Briery CM, Clokey D, Martin RW, Williford NJ, Bofill JA, Morrison JC. Metformin and insulin in the management of gestational diabetes mellitus: preliminary results of a comparison. J Reprod Med. 2007;52(11):1011-1015.

20. Rowan JA, Hague WM, Gao W, Battin MR, Moore MP. Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med. 2008;358(19):2003-15. doi: 10.1056/NEJMoa0707193

21. Tertti K, Ekblad U, Vahlberg T, Rönnemaa T. Comparison of metformin and insulin in the treatment of gestational diabetes: a retrospective, case-control study. Rev Diabet Stud. 2008;5(2):95-101. doi: 10.1900/RDS.2008.5.95

22. Balani J, Hyer SL, Rodin DA, Shehata H. Pregnancy outcomes in women with gestational diabetes treated with metformin or insulin: a case-control study. Diabet Med. 2009;26(8):798-802. doi: 10.1111/j.1464-5491.2009.02780.x

23. Ijäs H, Vääräsmäki M, Morin-Papunen L, Keravuo R, Ebeling T, Saarela T, Raudaskoski T. Metformin should be considered in the treatment of gestational diabetes: a prospective randomised study. BJOG. 2011;118(7):880-885. doi: 10.1111/j.1471-0528.2010.02763.x

24. Niromanesh S, Alavi A, Sharbaf FR, Amjadi N, Moosavi S, Akbari S. Metformin compared with insulin in the management of gestational diabetes: a randomized clinical trial. Diabetes Res Clin Pract. 2012;98(3):422-9. doi: 10.1016/j.diabres.2012.09.031

25. Tertti K, Ekblad U, Koskinen P, Vahlberg T, Rönnemaa T. Metformin vs insulin in gestational diabetes. A randomized study characterizing metformin patients needing additional insulin. Diabetes Obes Metab. 2013;15(3):246-251. doi: 10.1111/dom.12017

26. Spaulonci CP, Bernardes LS, Trindad TC, Zugaib M, Francisco RP. Randomized trial of metformin vs insulin in the management of gestational diabetes. Am J Obstet Gynecol. 2013;209(1):34.e1-7. doi: 10.1016/j.ajog.2013.03.022

27. Silva JC, Pacheco C, Bizato J, de Souza BV, Ribeiro TE, Bertini AM. Metformin compared to glyburide for the management of gestational diabetes. Int J Gynaecol Obstet. 2010;111(1):37-40. doi: 10.1016/j.ijgo.2010.04.028

28. Moore LE, Clokey D, Pappaport V, Curet LB. Metformin compared with glyburide in gestational diabetes. Obstet Gynecol. 2010;115(1):55-59. doi: 10.1097/AOG.0b013e3181c52132

29. Silva 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;40(3):225-228. doi: 10.1515/jpm-2011-0175

30. Bolton S, Cleary B, Walsh J, Dempsey E, Turner MJ. Continuation of metformin in the first trimester of women with polycystic ovarian syndrome is not associated with increased perinatal morbidity. Eur J Pediatr. 2009;168(2):203-206. doi: 10.1007/s00431-008-0737-7

31. Gilbert C, Valois M, Koren G. Pregnancy outcomes after first trimester exposure to metformin: a meta analysis. Fertil Steril. 2006 Sep;86(3):658-663.

32. Metformin. Drugs in Pregnancy and Lactation, 9th edition. Briggs GG, editor. Philadelphia, PA: Lippincott Williams & Wilkins; 2011. pages.pages 912-915.

33. Iljas H, Vaarasmaki M, Saarela T, Keravou R, Raudaskoski T. A follow-up of randomized study of metformin and insulin in gestational diabetes mellitus: growth and development of the children at the age of 18 months. BJOG. 2014 [in press]. doi: 10.1111/1471-0528.12964

34. Coustan DR, Lowe LP, Metzger BE, Dyer AR; International Association of Diabetes and Pregnancy Study Groups. The Hyperglycemia and adverse pregnancy outcome (HAPO) study: paving the way for new diagnostic criteria for gestational diabetes mellitus. Am J Obstet Gynecol. 2010;202(6):654.e1-6. doi: 10.1016/j.ajog.2010.04.006

35. International Association of Diabetes and Pregnancy Study Groups Consensus Panel, Metzger BE, Gabbe SG, Persson B, Buchanan TA, Catalano PA, Damm P, Dyer AR, Leiva Ad, Hod M, Kitzmiler JL, Lowe LP, McIntyre HD, Oats JJ, Omori Y, Schmidt MI. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010;33(3):676-82. doi: 10.2337/dc09-1848

36. Diagnostic Criteria and Classification of Hyperglycemia First Detected in Pregnancy. World Health Organization. (accessed September 22, 2014).

37. Acarbose. In: Drugs in Pregnancy and Lactation, 9th edition. Briggs GG, editor. Philadelphia, PA: Lippincott Williams & Wilkins; 2011. pages 5-6.

38. Bertini AM, Silva JC, Taborda W, Becker F, Lemos Bebber FR, Zucco Viesi JM, Aquim G, Engel Ribeiro T. Perinatal outcomes and the use of oral hypoglycemic agents. J Perinat Med. 2005;33(6):519-523.

39. Sitagliptin. In: Drugs in Pregnancy and Lactation, 9th edition. Briggs GG, editor. Philadelphia, PA: Lippincott Williams & Wilkins; 2011. pages 1337-1339.

40. Teelucksingh S, Youssef JE, Sohan K, Ramsewak S. Prolonged inadvertent pravastatin use in pregnancy. Reprod Toxicol. 2004;18(2):299-300.

41. Napoli A, Ciampa F, Colatrella A, Fallucca F. Use of repaglinide during the first weeks of pregnancy in two type 2 diabetic women. Diabetes Care. 2006;29(10):2326-2327.

42. Mollar-Puchades MA, Martin-Cortes A, Perez-Calvo A, Diaz-Garcia C. Use of repaglinide on a pregnant woment during embryogenesis. Diabetes Obes Metab. 2007;9(1):146-147.

43. Marshall V, Wilton L, Shakir S. Safety profile of repaglinide as used in general practice in England: results of a prescription-event monitoring study. Acta Diabetol. 2006;43(1):6-13.