Download PDF
Exp Clin Endocrinol Diabetes 2020; 128(03): 199-205
DOI: 10.1055/a-0603-3394
Meta-Analyses
© Georg Thieme Verlag KG Stuttgart · New York

The Effect of Metformin Therapy for Preventing Gestational Diabetes Mellitus in Women with Polycystic Ovary Syndrome: A Meta-Analysis

Jing Zhao
1   Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, China
,
Xiaoyan Liu
1   Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, China
,
Wenhua Zhang
1   Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, China
› Author Affiliations
Further Information

Publication History

received 12 November 2017
revised 22 March 2018

accepted 09 April 2018

Publication Date:
11 June 2018 (online)

Also available at
    Permissions and Reprints

Abstract

Objective This study was to analyze the efficacy of metformin intervention in preventing gestational diabetes mellitus (GDM).

Methods A systematic review and meta-analysis of clinical trials or observational studies of metformin intervention in preventing symptoms of GDM during pregnancy were performed. Medline, Embase, and Cochrane Library were searched through to now. The main evaluated primary outcomes were incident of GDM, miscarriage, preterm delivery, and neonatal mortality. The evaluated secondary outcomes were mean difference of gestational age at birth and birth weight between metformin group and control group.

Results We included 6 studies including 3 randomized clinical trials (RCTs), 2 observational studies, and 1 non-RCT in our meta-analysis. A total of 643 patients were enrolled for a follow-up study with continued metformin therapy (n=341) or not (n=302) during pregnancy. Metformin therapy reduced the proportion of patients developing GDM (log Odds Ratio: -1.27; 95%CI: -2.24 to -0.30) but had no significant effect on reducing the proportion of abortion, preterm delivery, and neonatal death in pregnant women with polycystic ovary syndrome (PCOS). Also, it did not cause a significant difference in gestational age at birth and birth weight in metformin group versus control/placebo group.

Conclusions Metformin was associated with less frequent GDM development than control diets, suggesting that it is the appropriate intervention to be prescribed to prevent GDM in patients with PCOS.

Key words

metformin - gestational diabetes mellitus (GDM) - polycystic ovary syndrome (PCOS) - meta-analysis
 

  • References

  • 1 Bentley-Lewis R, Levkoff S, Stuebe A. et al. Gestational diabetes mellitus: Postpartum opportunities for the diagnosis and prevention of type 2 diabetes mellitus. Nat Clin Pract Endocrinol Metab 2008; 4: 552-558
    CrossrefPubMedGoogle Scholar
  • 2 Gabbe SG, Graves CR. Management of diabetes mellitus complicating pregnancy. Obstet Gynecol 2003; 102: 857-868
    PubMedGoogle Scholar
  • 3 Petry CJ. Gestational diabetes: Risk factors and recent advances in its genetics and treatment. Br J Nutr 2010; 104: 775-787
    CrossrefPubMedGoogle Scholar
  • 4 Serlin DC, Lash RW. Diagnosis and management of gestational diabetes mellitus. Am Fam Physician 2009; 80: 57-62
    PubMedGoogle Scholar
  • 5 Teh WT, Teede HJ, Paul E. et al. Risk factors for gestational diabetes mellitus: Implications for the application of screening guidelines. Aust N Z J Obstet Gynaecol 2011; 51: 26-30
    CrossrefPubMedGoogle Scholar
  • 6 Sheehan MT. Polycystic ovarian syndrome: Diagnosis and management. Clin Med Res 2004; 2: 13-27
    CrossrefPubMedGoogle Scholar
  • 7 Koivusalo SB, Rono K, Klemetti MM. et al. Gestational Diabetes Mellitus Can Be Prevented by Lifestyle Intervention: The Finnish Gestational Diabetes Prevention Study (RADIEL): A Randomized Controlled Trial. Diabetes Care 2016; 39: 24-30
    CrossrefPubMedGoogle Scholar
  • 8 Bloomgarden ZT. Gestational diabetes mellitus and obesity. Diabetes Care 2010; 33: e60-e65
    CrossrefPubMedGoogle Scholar
  • 9 Bergel R, Hadar E, Toledano Y. et al. Pharmacological Management of Gestational Diabetes Mellitus. Curr Diab Rep 2016; 16: 118
    CrossrefPubMedGoogle Scholar
  • 10 Smoak IW, Sadler TW. Embryopathic effects of short-term exposure to hypoglycemia in mouse embryos in vitro. Am J Obstet Gynecol 1990; 163: 619-624
    CrossrefPubMedGoogle Scholar
  • 11 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
    CrossrefPubMedGoogle Scholar
  • 12 Dhulkotia JS, Ola B, Fraser R. et al. Oral hypoglycemic agents vs insulin in management of gestational diabetes: A systematic review and metaanalysis. Am J Obstet Gynecol 2010; 203: 457 e451-459
    PubMedGoogle Scholar
  • 13 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: 282-286
    CrossrefPubMedGoogle Scholar
  • 14 Nawaz FH, Khalid R, Naru T. et al. Does continuous use of metformin throughout pregnancy improve pregnancy outcomes in women with polycystic ovarian syndrome?. J Obstet Gynaecol Res 2008; 34: 832-837
    CrossrefPubMedGoogle Scholar
  • 15 Vanky E, Stridsklev S, Heimstad R. et al. Metformin versus placebo from first trimester to delivery in polycystic ovary syndrome: A randomized, controlled multicenter study. J Clin Endocrinol Metab 2010; 95: E448-E455
    CrossrefPubMedGoogle Scholar
  • 16 Vanky E, Salvesen KA, Heimstad R. et al. Metformin reduces pregnancy complications without affecting androgen levels in pregnant polycystic ovary syndrome women: Results of a randomized study. Hum Reprod 2004; 19: 1734-1740
    CrossrefPubMedGoogle Scholar
  • 17 Glueck CJ, Pranikoff J, Aregawi D. et al. Prevention of gestational diabetes by metformin plus diet in patients with polycystic ovary syndrome. Fertil Steril 2008; 89: 625-634
    CrossrefPubMedGoogle Scholar
  • 18 Glueck CJ, Wang P, Kobayashi S. et al. Metformin therapy throughout pregnancy reduces the development of gestational diabetes in women with polycystic ovary syndrome. Fertil Steril 2002; 77: 520-525
    CrossrefPubMedGoogle Scholar
  • 19 Abd El Hameed AA, Shreif HE, Mowafy HE. The role of continuing metformin therapy during pregnancy in the reduction of gestational diabetes and improving pregnancy outcomes in women with polycystic ovary syndrome. Middle East Fertility Society Journal 2011; 16: 204-208
    CrossrefPubMedGoogle Scholar
  • 20 Foroozanfard F, Moosavi SG, Mansouri F. et al. Obstetric and Neonatal Outcome in PCOS with Gestational Diabetes Mellitus. J Family Reprod Health 2014; 8: 7-12
    PubMedGoogle Scholar
  • 21 Dahlgren E, Johansson S, Lindstedt G. et al. Women with polycystic ovary syndrome wedge resected in 1956 to 1965: A long-term follow-up focusing on natural history and circulating hormones. Fertil Steril 1992; 57: 505-513
    CrossrefPubMedGoogle Scholar
  • 22 Haakova L, Cibula D, Rezabek K. et al. Pregnancy outcome in women with PCOS and in controls matched by age and weight. Hum Reprod 2003; 18: 1438-1441
    CrossrefPubMedGoogle Scholar
  • 23 Lanzone A, Fulghesu AM, Guido M. et al. Differential androgen response to adrenocorticotropic hormone stimulation in polycystic ovarian syndrome: Relationship with insulin secretion. Fertil Steril 1992; 58: 296-301
    CrossrefPubMedGoogle Scholar
  • 24 Morin-Papunen LC, Vauhkonen I, Koivunen RM. et al. Insulin sensitivity, insulin secretion, and metabolic and hormonal parameters in healthy women and women with polycystic ovarian syndrome. Hum Reprod 2000; 15: 1266-1274
    CrossrefPubMedGoogle Scholar
  • 25 Lankarani M, Valizadeh N, Heshmat R et al. Evaluation of dyslipidemia in polycystic ovary syndrome. 2005;
    PubMed
  • 26 Motta AB. Mechanisms involved in metformin action in the treatment of polycystic ovary syndrome. Curr Pharm Des 2009; 15: 3074-3077
    CrossrefPubMedGoogle Scholar
  • 27 Kirpichnikov D, McFarlane SI, Sowers JR. Metformin: An update. Ann Intern Med 2002; 137: 25-33
    PubMedGoogle Scholar
  • 28 Diamanti-Kandarakis E, Christakou CD, Kandaraki E. et al. Metformin: An old medication of new fashion: Evolving new molecular mechanisms and clinical implications in polycystic ovary syndrome. Eur J Endocrinol 2010; 162: 193-212
    CrossrefPubMedGoogle Scholar
  • 29 Velazquez EM, Mendoza S, Hamer T. et al. Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy. Metabolism 1994; 43: 647-654
    CrossrefPubMedGoogle Scholar