Vol 71, No 2 (2020)
Review paper
Published online: 2020-04-29

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Metformin therapy in pregnancy [Zastosowanie metforminy w ciąży]

Joanna Krupej- Kędzierska12, Edyta Cichocka1, Leszek Kędzierski3, Bogusław Okopień2, Janusz Gumprecht1
Pubmed: 32396212
Endokrynol Pol 2020;71(2):184-195.


Gestational diabetes mellitus (GDM), i.e. a carbohydrate metabolism disorder at pregnancy, is one of the most common metabolic complications that occur during this period. Pancreatic b-cell dysfunction and insulin resistance during pregnancy are considered the main causes of the condition. It is currently estimated that GDM is confirmed in 1–25% of patients. Diagnosis and appropriate management allow to reduce the risk of complications in newborns and the perinatal mortality rate and also improve the prognosis for mother and offspring. Metformin is taken by many patients before pregnancy due to both previously diagnosed type 2 diabetes and in the treatment of prediabetes, obesity and polycystic ovary syndrome (PCOS) as part of therapy for insulin resistance. The use of metformin in pregnancy has been controversial for many years, particularly in terms of the safety of continuation of drug therapy. Available scientific data indicate both benefits and possible drug-related adverse effects in offspring of metformin-treated patients. This problem is related not only to patients with type 2 diabetes, but also to those with PCOS who are at increased risk of miscarriage, preterm delivery and the diagnosis of GDM in subsequent stages of pregnancy. Conclusive and uniform recommendations for the use of metformin at each stage of pregnancy have not been established yet due to the doubts about the mechanisms of action of the drug, particularly at the cellular level. This review paper presents the current state of knowledge on the use of metformin during pregnancy.

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  1. Chiefari E, Arcidiacono B, Foti D, et al. Gestational diabetes mellitus: an updated overview. J Endocrinol Invest. 2017; 40(9): 899–909.
  2. Doi SAR, Furuya-Kanamori L, Toft E, et al. Metformin in pregnancy to avert gestational diabetes in women at high risk: Meta-analysis of randomized controlled trials. Obes Rev. 2020; 21(1): e12964.
  3. McIntyre HD, Catalano P, Zhang C, et al. Gestational diabetes mellitus. Nat Rev Dis Primers. 2019; 5(1): 47.
  4. Cea-Soriano L, García-Rodríguez LA, Brodovicz KG, et al. Safety of non-insulin glucose-lowering drugs in pregnant women with pre-gestational diabetes: A cohort study. Diabetes Obes Metab. 2018; 20(7): 1642–1651.
  5. Bao LX, Shi WT, Han YX. Metformin versus insulin for gestational diabetes: a systematic review and meta-analysis. J Matern Fetal Neonatal Med. 2019 [Epub ahead of print]: 1–13.
  6. Gonzalez CD, Alvariñas J, Bagnes MFG, et al. Metformin and Pregnancy Outcomes: Evidence Gaps and Unanswered Questions. Curr Clin Pharmacol. 2019; 14(1): 54–60.
  7. Tarry-Adkins JL, Aiken CE, Ozanne SE. Neonatal, infant, and childhood growth following metformin versus insulin treatment for gestational diabetes: A systematic review and meta-analysis. PLoS Med. 2019; 16(8): e1002848.
  8. Ainuddin JA, Karim N, Zaheer S, et al. 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.
  9. Milewicz A, Kudła M, Spaczyński RZ, et al. The polycystic ovary syndrome: a position statement from the Polish Society of Endocrinology, the Polish Society of Gynaecologists and Obstetricians, and the Polish Society of Gynaecological Endocrinology. Endokrynol Pol. 2018; 69(4).
  10. Cassina M, Donà M, Di Gianantonio E, et al. First-trimester exposure to metformin and risk of birth defects: a systematic review and meta-analysis. Hum Reprod Update. 2014; 20(5): 656–669.
  11. Barbour LA, Feig DS, Barbour LA, et al. Metformin for Gestational Diabetes Mellitus: Progeny, Perspective, and a Personalized Approach. Diabetes Care. 2019; 42(3): 396–399.
  12. Lindsay RS, Loeken MR. Metformin use in pregnancy: promises and uncertainties. Diabetologia. 2017; 60(9): 1612–1619.
  13. Standards of Medical Care in Diabetes. Diab Care. 2004; 28(Suppl 1): S4–S36.
  14. PTD Z. Zalecenia PTD. 2017 Guidelines on the management of diabetic patients. A position of Diabetes Poland. Clin Diab. 2017; 6(A): 1–80.
  15. Romero R, Erez O, Hüttemann M, et al. Metformin, the aspirin of the 21st century: its role in gestational diabetes mellitus, prevention of preeclampsia and cancer, and the promotion of longevity. Am J Obstet Gynecol. 2017; 217(3): 282–302.
  16. Kumar R, Lowe J, Thompson-Hutchison F, et al. Implementation and Evaluation of the "Metformin First" Protocol for Management of Gestational Diabetes. Can J Diabetes. 2019; 43(8): 554–559.
  17. Tarry-Adkins JL, Aiken CE, Ozanne SE. Neonatal, infant, and childhood growth following metformin versus insulin treatment for gestational diabetes: A systematic review and meta-analysis. PLoS Med. 2019; 16(8): e1002848.
  18. Hu G, Bouchard C, Bray GA, et al. Trunk versus extremity adiposity and cardiometabolic risk factors in white and African American adults. Diabetes Care. 2011; 34(6): 1415–1418.
  19. Nanovskaya TN, Nekhayeva IA, Patrikeeva SL, et al. Transfer of metformin across the dually perfused human placental lobule. Am J Obstet Gynecol. 2006; 195(4): 1081–1085.
  20. 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): 2003–2015.
  21. Rowan JA. MiG Investigators. 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–S219.
  22. Ijäs H, Vääräsmäki M, Saarela T, et al. A follow-up of a randomised study of metformin and insulin in gestational diabetes mellitus: growth and development of the children at the age of 18 months. BJOG. 2015; 122(7): 994–1000.
  23. Tertti K, Eskola E, Rönnemaa T, et al. Neurodevelopment of Two-Year-Old Children Exposed to Metformin and Insulin in Gestational Diabetes Mellitus. J Dev Behav Pediatr. 2015; 36(9): 752–757.
  24. Xu Q, Xie Q. Long-term effects of prenatal exposure to metformin on the health of children based on follow-up studies of randomized controlled trials: a systematic review and meta-analysis. Arch Gynecol Obstet. 2019; 299(5): 1295–1303.
  25. Rowan JA, Rush EC, Plank LD, et al. Metformin in gestational diabetes: the offspring follow-up (MiG TOFU): body composition and metabolic outcomes at 7-9 years of age. BMJ Open Diabetes Res Care. 2018; 6(1): e000456.
  26. Diav-Citrin O, Steinmetz-Shoob S, Shechtman S, et al. In-utero exposure to metformin for type 2 diabetes or polycystic ovary syndrome: A prospective comparative observational study. Reprod Toxicol. 2018; 80: 85–91.
  27. Hjorth-Hansen A, Salvesen Ø, Engen Hanem LG, et al. Fetal Growth and Birth Anthropometrics in Metformin-Exposed Offspring Born to Mothers With PCOS. J Clin Endocrinol Metab. 2018; 103(2): 740–747.
  28. Piacquadio K, Hollingsworth DR, Murphy H. Effects of in-utero exposure to oral hypoglycaemic drugs. Lancet. 1991; 338(8771): 866–869.
  29. Coetzee EJ. Counterpoint: Oral hypoglyemic agents should be used to treat diabetic pregnant women. Diabetes Care. 2007; 30(11): 2980–2982.
  30. Coetzee EJ, Jackson WP. Metformin in management of pregnant insulin-independent diabetics. Diabetologia. 1979; 16(4): 241–245.
  31. Begum MR, Khanam NN, Quadir E, et al. Prevention of gestational diabetes mellitus by continuing metformin therapy throughout pregnancy in women with polycystic ovary syndrome. J Obstet Gynaecol Res. 2009; 35(2): 282–286.
  32. Hanem LG, Stridsklev S, Júlíusson PB, et al. Metformin Use in PCOS Pregnancies Increases the Risk of Offspring Overweight at 4 Years of Age: Follow-Up of Two RCTs. J Clin Endocrinol Metab. 2018; 103(4): 1612–1621.
  33. Løvvik TS, Carlsen SM, Salvesen Ø, et al. Use of metformin to treat pregnant women with polycystic ovary syndrome (PregMet2): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2019; 7(4): 256–266.
  34. Valdés E, Sepúlveda-Martínez A, Candia P, et al. Metformin as a prophylactic treatment of gestational diabetes in pregnant patients with pregestational insulin resistance: A randomized study. J Obstet Gynaecol Res. 2018; 44(1): 81–86.