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The role of adding metformin in insulin-resistant diabetic pregnant women: a randomized controlled trial

  • Maternal-Fetal Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

The aim of the present study is to assess the impact of adding oral metformin to insulin therapy in pregnant women with insulin-resistant diabetes mellitus.

Methods

The current non-inferiority randomized controlled trial was conducted at Ain Shams University Maternity Hospital. The study included pregnant women with gestational or pre-existing diabetes mellitus at gestations between 20 and 34 weeks, who showed insulin resistance (defined as poor glycemic control at a daily dose of ≥1.12 units/kg). Recruited women were randomized into one of two groups: group I, including women who received oral metformin without increasing the insulin dose; and group II, including women who had their insulin dose increased. The primary outcome was maternal glycemic control. Secondary outcomes included maternal bouts of hypoglycemia, need for another hospital admission for uncontrolled diabetes during pregnancy, gestational age at delivery, mode of delivery, birth weight, birth trauma, congenital anomalies, 1- and 5-min Apgar score, neonatal hypoglycemia, need for neonatal intensive care unit (NICU) admission and adverse neonatal outcomes.

Results

A total number of 154 women with diabetes mellitus with pregnancy were approached; of them 90 women were eligible and were randomly allocated and included in the final analysis. The recruited 90 women were randomized into one of two groups: group I (metformin group) (n = 46), including women who received oral metformin in addition to the same initial insulin dose; and group II (control group) (n = 44), including women who had their insulin dose increased according to the standard protocol. The mean age of included women was 29.84 ± 5.37 years (range 20–42 years). The mean gestational age at recruitment was 28.7 ± 3.71 weeks (range 21–34 weeks). Among the 46 women of group I, 17 (36.9 %) women reached proper glycemic control at a daily metformin dose of 1,500 mg, 18 (39.2 %) at a daily dose of 2,000 mg, while 11 (23.9 %) received metformin at a daily dose of 2,000 mg without reaching proper glycemic control and needed raising the dose of insulin dose.

Conclusion

Adding metformin to insulin therapy in women with insulin-resistant diabetes mellitus with pregnancy seems to be effective in proper glycemic control in a considerable proportion of women, along with benefits of reduced hospital stay, reduced frequency of maternal hypoglycemia as well as reduced frequency of neonatal hypoglycemia, NICU admission and neonatal respiratory distress syndrome.

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Abbreviations

AMP:

Adenosine monophosphate

ASD:

Atrial septal defect

BMI:

Body mass index

DM:

Diabetes mellitus

FDA:

Food and drug administration

GDM:

Gestational DM

GIR:

Glucose–insulin ratio

HOMA-IR:

Homeostatic model assessment of insulin resistance

IQR:

Interquartile range

NICU:

Neonatal intensive care unit

NNH:

Number needed to harm

NNT:

Number needed to treat

NPH:

Neutral protamine Hagedorn

PCOS:

Polycystic ovarian syndrome

PDM:

Pre-existing DM

QUICKI:

Quantitative insulin sensitivity check index

References

  1. Hedley AA, Ogden CL, Johnson CL (2004) Prevalence of overweight and obesity among US children, adolescents and adults, 1999–2002. JAMA 291:2847–2850

    Article  CAS  PubMed  Google Scholar 

  2. Metzger BE, Buchanan TA, Coustan DR, de Leiva A, Dunger DB, Hadden DR et al (2007) Summary and recommendations of the fifth international workshop-conference on gestational diabetes mellitus. Diabetes Care 30(Suppl 2):S251–S260

    Article  CAS  PubMed  Google Scholar 

  3. Butte N (2000) Carbohydrates and lipid metabolism inpregnancy: normal compared with gestational diabetes mellitus. Am J Clin Nutr 71:1256–1261

    Google Scholar 

  4. Pridjian G, Benjamin TD (2010) Update on gestational diabetes. Obstet Gynecol Clin N Am 37:255–267

    Article  Google Scholar 

  5. ACOG Practice Bulletin No. 30 (2001) American College of Obstetricians and Gynecologists. Gestational diabetes. Obstet Gynecol 98:525–538

    Google Scholar 

  6. Rowan JA, Hague WM, Gao W, Moore MP (2008) Metformin versus insulin for treatment of gestational diabetes. N Eng J Med 358:2003–2015

    Article  CAS  Google Scholar 

  7. Shao J, Catalano PM, Yamashita H (2000) Impaired insulin receptor tyrosine kinase activity in skeletal muscle from normal pregnant women and women with gestational diabetes. Diabetes 49:603–610

    Article  CAS  PubMed  Google Scholar 

  8. Kirwan JP, Hauguel-de Mouson S, Lepercq J (2002) TNF alpha is a predictor of insulin resistance in human pregnancy. Diabetes 51:2207–2213

    Article  CAS  PubMed  Google Scholar 

  9. Moore LE, Clokey D, Rappaport VJ (2010) Metformincompared with glyburide in gestational diabetes, arandomized controlled trial. Obstet Gynecol 115:55–59

    Article  CAS  PubMed  Google Scholar 

  10. Misso ML, Costello MF, Garrubba M, Wong J, Hart R, Rombauts L et al (2013) Metformin versus clomiphene citrate for infertility in non-obese women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update 19(1):2–11

    Article  CAS  PubMed  Google Scholar 

  11. Morin-Papunen L, Rantala AS, Unkila-Kallio L, Tiitinen A, Hippeläinen M, Perheentupa A et al (2012) Metformin improves pregnancy and live-birth rates in women with polycystic ovary syndrome (PCOS): a multicenter, double-blind, placebo-controlled randomized trial. J Clin Endocrinol Metab 97(5):1492–1500

    Article  CAS  PubMed  Google Scholar 

  12. de Oliveira Baraldi C, Lanchote VL, de Jesus Antunes N, de Jesus Ponte Carvalho TM, Dantas Moisés EC, Duarte G, Cavalli RC (2011) Metformin pharmacokinetics in non diabetic pregnant women with polycystic ovary syndrome. Eur J Clin Pharmacol 67(10):1027–1033

    Article  PubMed  Google Scholar 

  13. Glueck CJ, Goldenberg P, Wang M, Loftspring M, Sherman A (2004) Metformin during pregnancy reduces insulin, insulin resistance, insulin secretion, weight, testosterone and development of gestational diabetes: prospective longitudinal assessment of women with polycystic ovary syndrome from preconception throughout pregnancy. Hum Reprod 19(3):510–521

    Article  CAS  PubMed  Google Scholar 

  14. Silva JC, Pacheco C, Bizato J, de Souza BV, Ribeiro TE, Bertini AM (2010) Metformin compared with glyburide for the management of gestational diabetes. Int J Gynaecol Obstet 111(1):37–40

    Article  CAS  PubMed  Google Scholar 

  15. Silva JC, Fachin DR, Coral MI, Bertini AM (2012) Perinatal impact of the use of metformin and glyburide for the treatment of gestational diabetes mellitus. J Perinatal Med 40(3):225–228

    Article  CAS  Google Scholar 

  16. Norman RJ, Wang JX, Hague W (2004) Should we continue or stop insulin sensitizing drugs during pregnancy. Curr Opin Obstet Gynecol 16(3):245–250

    Article  PubMed  Google Scholar 

  17. Homko CJ, Sivan E, Reece AE (2004) Is there a role for oral antihyperglycemics in gestational diabetes and type 2 diabetes during pregnancy. Treat Endocrinol 3(3):133–139

    Article  CAS  PubMed  Google Scholar 

  18. Kapoor N, Sankaran S, Hyer S, Shehata H (2007) Diabetes in pregnancy: a review of current evidence. Curr Opin Obstet Gynecol 19(6):586–590

    Article  PubMed  Google Scholar 

  19. Maymone AC, Baillargeon JP, Menard J, Ardilouze JL (2011) Oral hypoglycemic agents for gestational diabetes mellitus. Expert Opin Drug Saf 10(2):227–238

    Article  CAS  PubMed  Google Scholar 

  20. Ijas H, Vaarasmaki M, Morin-Papunen L, Keravuo R, Ebeling T, Saarela T et al (2011) Metformin should be considered in the treatment of gestational diabetes: a prospective randomized study. BJOG 118(7):880–885

    Article  CAS  PubMed  Google Scholar 

  21. Niromanesh S, Alavi A, Sharbaf FR, Amjadi N, Moosavi S, Akbari S (2012) Metformin compared with insulin in the management of gestational diabetes mellitus: a randomized clinical trial. Diabetes Res Clin Pract 98(3):422–429

    Article  CAS  PubMed  Google Scholar 

  22. Hickman MA, McBride R, Boggess KA, Strauss R (2013) Metformin compared with insulin in the treatment of pregnant women with overt diabetes: a randomized controlled trial. Am J Perinatol 30(6):483–490

    Article  PubMed  Google Scholar 

  23. Simmons D, Walters BN, Roman JA, Mclntyre HD (2004) Metformin therapy and diabetes in pregnancy. Med J Aust 180(9):462–464

    PubMed  Google Scholar 

  24. Monzillo LU, Hamdy O (2003) Evaluation of insulin sensitivity in clinical practice and in research settings. Nutr Rev 61(12):397–412

    Article  PubMed  Google Scholar 

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Conflict of interest

The authors reported no conflict of interest. All the authors had substantial contributions to conception and design, acquisition of data, analysis and interpretation of data, drafting and revising the article critically with final approval of the version to be published. The research was funded by the authors.

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Authors and Affiliations

  1. Ain-Shams Faculty of Medicine, Abbasiya Square, Cairo, Egypt

    Moustafa Ibrahim Ibrahim, Ahmed Hamdy, Adel Shafik, Salah Taha & Mohammed Faris

  2. Resident of Gynecology, Gynecological Oncology Unit, Ain Shams University Maternity Hospital, Cairo, Egypt

    Mohammed Anwar

Authors
  1. Moustafa Ibrahim Ibrahim
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  2. Ahmed Hamdy
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  3. Adel Shafik
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  4. Salah Taha
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  5. Mohammed Anwar
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  6. Mohammed Faris
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Correspondence to Moustafa Ibrahim Ibrahim.

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Ibrahim, M.I., Hamdy, A., Shafik, A. et al. The role of adding metformin in insulin-resistant diabetic pregnant women: a randomized controlled trial. Arch Gynecol Obstet 289, 959–965 (2014). https://doi.org/10.1007/s00404-013-3090-7

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  • DOI: https://doi.org/10.1007/s00404-013-3090-7

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