Skip to main content
SpringerLink
Log in

Metformin in Pregnancy for Women with Type 2 Diabetes: a Review

  • Diabetes and Pregnancy (M-F Hivert and CE Powe, Section Editors)
  • Published:
Current Diabetes Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

To review the current evidence for the use of metformin in pregnancy for women with type 2 diabetes.

Recent Findings

A large, multicenter, double-blind randomized controlled trial found that women with type 2 diabetes in pregnancy treated with metformin as an adjunct to insulin therapy had less gestational weight gain, insulin requirements, caesarian sections, macrosomia, and neonatal adiposity, but more neonates were small for gestational age (SGA) compared with insulin alone. It is unclear if the higher number of SGA infants are a direct result of metformin exposure or mediated through other effects such as less gestational weight gain and improved glycemic control. Additional follow-up studies of offspring exposed to metformin in utero are required.

Summary

Metformin may be a useful adjunctive treatment for women with type 2 diabetes in pregnancy to help meet glycemic targets if there are no concerns for or indications of SGA.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Lin X, Xu Y, Pan X, Xu J, Ding Y, Sun X, et al. Global, regional, and national burden and trend of diabetes in 195 countries and territories: an analysis from 1990 to 2025. Sci Rep. 2020;10(1):14790. https://doi.org/10.1038/s41598-020-71908-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Mackin ST, Nelson SM, Kerssens JJ, Wood R, Wild S, Colhoun HM, et al. Diabetes and pregnancy: national trends over a 15 year period. Diabetologia. 2018;61(5):1081–8. https://doi.org/10.1007/s00125-017-4529-3.

    Article  PubMed  PubMed Central  Google Scholar 

  3. 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. https://doi.org/10.1136/bmj.38856.692986.AE.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Tennant PW, Glinianaia SV, Bilous RW, Rankin J, Bell R. Pre-existing diabetes, maternal glycated haemoglobin, and the risks of fetal and infant death: a population-based study. Diabetologia. 2014;57(2):285–94. https://doi.org/10.1007/s00125-013-3108-5.

    Article  CAS  PubMed  Google Scholar 

  5. Murphy HR, Howgate C, O’Keefe J, Myers J, Morgan M, Coleman MA, et al. Characteristics and outcomes of pregnant women with type 1 or type 2 diabetes: a 5-year national population-based cohort study. Lancet Diabetes Endocrinol. 2021;9(3):153–64. https://doi.org/10.1016/S2213-8587(20)30406-X.

    Article  PubMed  Google Scholar 

  6. LaMoia TE, Shulman GI. Cellular and molecular mechanisms of metformin action. Endocr Rev. 2021;42(1):77–96. https://doi.org/10.1210/endrev/bnaa023.

    Article  PubMed  Google Scholar 

  7. Feig DS, Donovan LE, Zinman B, Sanchez JJ, Asztalos E, Ryan EA, et al. Metformin in women with type 2 diabetes in pregnancy (MiTy): a multicentre, international, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2020;8(10):834–44. https://doi.org/10.1016/S2213-8587(20)30310-7.

    Article  CAS  PubMed  Google Scholar 

  8. Viollet B, Guigas B, Sanz Garcia N, Leclerc J, Foretz M, Andreelli F. Cellular and molecular mechanisms of metformin: an overview. Clin Sci (Lond). 2012;122(6):253–70. https://doi.org/10.1042/CS20110386.

    Article  CAS  Google Scholar 

  9. Hyer S, Balani J, Shehata H. Metformin in pregnancy: mechanisms and clinical applications. Int J Mol Sci. 2018;19(7). doi:https://doi.org/10.3390/ijms19071954.

  10. Cassina M, Dona M, Di Gianantonio E, Litta P, Clementi M. First-trimester exposure to metformin and risk of birth defects: a systematic review and meta-analysis. Hum Reprod Update. 2014;20(5):656–69. https://doi.org/10.1093/humupd/dmu022.

    Article  CAS  PubMed  Google Scholar 

  11. 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. Can J Clin Pharmacol. 2003;10(4):179–83.

    PubMed  Google Scholar 

  12. Feig DS, Berger H, Donovan L, Godbout A, Kader T, Keely E, et al. Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: diabetes and pregancy. Can J Diabetes. 2018;42(18):S255–82.

    Article  PubMed  Google Scholar 

  13. Zhao LP, Sheng XY, Zhou S, Yang T, Ma LY, Zhou Y, et al. Metformin versus insulin for gestational diabetes mellitus: a meta-analysis. Br J Clin Pharmacol. 2015;80(5):1224–34. https://doi.org/10.1111/bcp.12672.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Balsells M, Garcia-Patterson A, Sola I, Roque M, Gich I, Corcoy R. Glibenclamide, metformin, and insulin for the treatment of gestational diabetes: a systematic review and meta-analysis. BMJ. 2015;350: h102. https://doi.org/10.1136/bmj.h102.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Jiang YF, Chen XY, Ding T, Wang XF, Zhu ZN, Su SW. Comparative efficacy and safety of OADs in management of GDM: network meta-analysis of randomized controlled trials. J Clin Endocrinol Metab. 2015;100(5):2071–80. https://doi.org/10.1210/jc.2014-4403.

    Article  CAS  PubMed  Google Scholar 

  16. Poolsup N, Suksomboon N, Amin M. Efficacy and safety of oral antidiabetic drugs in comparison to insulin in treating gestational diabetes mellitus: a meta-analysis. PLoS ONE. 2014;9(10): e109985. https://doi.org/10.1371/journal.pone.0109985.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kitwitee P, Limwattananon S, Limwattananon C, Waleekachonlert O, Ratanachotpanich T, Phimphilai M, et al. Metformin for the treatment of gestational diabetes: an updated meta-analysis. Diabetes Res Clin Pract. 2015;109(3):521–32. https://doi.org/10.1016/j.diabres.2015.05.017.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  19. 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. https://doi.org/10.1371/journal.pone.0125712.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. 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. Am J Perinatol. 2013;30(6):483–90. https://doi.org/10.1055/s-0032-1326994.

    Article  PubMed  Google Scholar 

  21. 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. Am J Perinatol. 2015;30(2):163–70. https://doi.org/10.1055/s-0034-1378144.

    Article  PubMed  Google Scholar 

  22. 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. Arch Gynecol Obstet. 2014;289(5):959–65. https://doi.org/10.1007/s00404-013-3090-7.

    Article  CAS  PubMed  Google Scholar 

  23. 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. J Diabetes Res. 2015;2015: 325851. https://doi.org/10.1155/2015/325851.

    Article  PubMed  PubMed Central  Google Scholar 

  24. 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. Diabet Med. 2017;34(1):27–36. https://doi.org/10.1111/dme.13150.

    Article  CAS  PubMed  Google Scholar 

  25. National Institute for Health and Care Excellence. Diabetes in pregnancy: management from preconception to the postnatal period. NICE 2020. https://www.nice.org.uk/guidance/ng3/resources/diabetes-in-pregnancy-management-from-preconception-to-the-postnatal-period-pdf-51038446021. Accessed March 7 2021.

  26. Berry DC, Thomas SD, Dorman KF, Ivins AR, de Los Angeles Abreu M, Young L et al. Rationale, design, and methods for the medical optimization and management of pregnancies with overt type 2 diabetes (MOMPOD) study. BMC Pregnancy Childbirth. 2018;18(1):488. doi:https://doi.org/10.1186/s12884-018-2108-3.

  27. Boggess K. Medical optimization of management of type 2 diabetes complicating pregnancy (MOMPOD). U.S. National Library of Medicine. 2016. https://clinicaltrials.gov/ct2/show/NCT02932475. Accessed March 19 2021.

  28. van Weelden W, Wekker V, de Wit L, Limpens J, Ijas H, van Wassenaer-Leemhuis AG, et al. Long-term effects of oral antidiabetic drugs during pregnancy on offspring: a systematic review and meta-analysis of follow-up studies of RCTs. Diabetes Ther. 2018;9(5):1811–29. https://doi.org/10.1007/s13300-018-0479-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Landi SN, Radke S, Engel SM, Boggess K, Sturmer T, Howe AS, et al. Association of long-term child growth and developmental outcomes with metformin vs insulin treatment for gestational diabetes. JAMA Pediatr. 2019;173(2):160–8. https://doi.org/10.1001/jamapediatrics.2018.4214.

    Article  PubMed  Google Scholar 

  30. Feig DS. MiTy Kids (metformin in women with type 2 diabetes in pregnancy kids trial). U.S. National Library of Medicine. 2013. https://clinicaltrials.gov/ct2/show/NCT01832181. Accessed March 5 2021.

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

    Jamie L. Benham, Lois E. Donovan & Jennifer M. Yamamoto

  2. Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

    Jamie L. Benham

  3. Department of Obstetrics and Gynecology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

    Lois E. Donovan

  4. Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, Canada

    Lois E. Donovan

  5. Department of Internal Medicine, Children’s Hospital Research Institute of Manitoba, University of Manitoba, Room 836, 715 McDermot Ave, Winnipeg, MB, R3E3P4, Canada

    Jennifer M. Yamamoto

Authors
  1. Jamie L. Benham
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lois E. Donovan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jennifer M. Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jennifer M. Yamamoto.

Ethics declarations

Conflict of Interest

The authors declare no competing interests.

Human and Animal Rights

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Benham, J.L., Donovan, L.E. & Yamamoto, J.M. Metformin in Pregnancy for Women with Type 2 Diabetes: a Review. Curr Diab Rep 21, 36 (2021). https://doi.org/10.1007/s11892-021-01409-0

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11892-021-01409-0

Keywords

Search

Navigation