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The Effect of Metformin On Patients Who Are Pregnant and Have PCOS

Mar 19, 2019
 
Editor: Joy Pape, MSN, FNP-C, CDE, WOCN, CFCN, FAADE

Author: Ghazal Blair, Pharm.D. Candidate 2019, LECOM School of Pharmacy

Treatment throughout pregnancy may reduce rate of miscarriage or preterm delivery.

Polycystic ovary syndrome (PCOS) is a medical condition that causes hormone imbalance and metabolic changes, and affects 1 in 10 women. The disturbances caused by PCOS are seen in reproductive hormones and can lead to a variety of complications, including menstrual irregularity, androgen excess, and resistance to insulin. Therefore, patients with PCOS are at a greater risk of developing diabetes, cardiovascular disease, and complications during pregnancy.

 

The high rate of miscarriage is one of the most common adverse events associated with PCOS. Metformin is an antidiabetic medication that is prescribed as a second-line treatment option for patients with PCOS when type 2 diabetes and glucose intolerance are present. Additionally, metformin is used for the treatment of menstrual irregularity in women with PCOS who have not been diagnosed with diabetes when treatment with hormonal contraceptives fails or is contraindicated.

An Epi-analysis, published in 2012, focused on re-evaluating the effect of metformin on decreasing late miscarriage and preterm delivery, pre-eclampsia and gestational diabetes in women with PCOS. This epi-analysis included two randomized trials on metformin versus placebo with a total of 313 participants ages 18-42. Results from data analysis showed patients who were treated with metformin had a lower rate of late miscarriage and preterm delivery compared to patients in the placebo group (p < 0.01). On the other hand, the difference in the incidence of gestational diabetes and pre-eclampsia was not significant between the metformin and the placebo group. This epi‐analysis concluded that metformin treatment during pregnancy appears to decrease preterm delivery in patients with PCOS.

PregMet2 is a recent study published in The Lancet Diabetes & Endocrinology, February of 2019. The general focus of PregMet2 is to examine if treatment with metformin from the first trimester of pregnancy until delivery is able to prevent late miscarriages and preterm deliveries in patients who are pregnant and have PCOS. This study is a randomized, placebo-controlled, double-blind, multicenter trial, which was conducted at 14 hospitals in Norway, Sweden, and Iceland. All 489 participants in this study met the inclusion criteria of having PCOS and singleton pregnancy, ages 18 to 45 years old.

This study randomized subjects with a 1:1 ratio into two groups. The study group received metformin 500mg tablet twice a day for the first week and then increased to 2 tablets twice daily from the second week to delivery. The placebo group received placebo, following the exact routine. To assure masking, all parties involved in the study, including participants, care providers, investigators, and outcome evaluators, were blinded.

PregMet2 defined the primary endpoints as a combined incidence of late miscarriages from week 13 to week 22, and preterm births from week 23 to week 36. Secondary endpoints included admission to NICU and a total number of days spent in NICU, the incidence of gestational diabetes, and pre-eclampsia. This study included a post-hoc individual participant data analysis of pregnancy outcomes. Post-hoc data analysis contained pooled data from the two previous randomized trials and the present study.

The results of data analysis showed that 5% of individuals in the metformin groups experienced a composite primary outcome of late miscarriage and preterm birth compared to 10% of participants in the placebo group (p=0·08). It was also noted that there was no significant difference between both groups for secondary endpoints, including the incidence of gestational diabetes (p=0·75). Furthermore, the results of the post-hoc pooled data analysis of individual participants presented that the late miscarriage or preterm delivery occurred in 5% of participants in the metformin group compared to 10% in the placebo group (p=0·004).

In conclusion, this study suggested that though metformin treatment from the late first trimester until delivery does not prevent gestational diabetes or pre-eclampsia, it may decrease the risk of late miscarriage and preterm birth in patients who are pregnant and have PCOS. Additionally, thorough care and observation should be performed during pregnancy for patients with PCOS since they are more at risk of serious pregnancy complications.

Practice Pearls:

  • Metformin treatment from the first trimester of pregnancy to delivery in patients who have PCOS may reduce the rate of miscarriage or preterm delivery.
  • Metformin treatment does not show to have any effects on reducing the prevalence of gestational diabetes in patients who are pregnant and have PCOS.
  • Metformin treatment does not show to have any effects on reducing the prevalence of pre-eclampsia in patients who are pregnant and have PCOS.

References:

“Polycystic Ovary Syndrome (PCOS).” Female Pelvic Medicine and Reconstructive Surgery, obgyn.ucla.edu/pcos.

Vanky E, De Zegher F,D ́ıaz M, Ib ́a ̃nez L, Carlsen SM. On the potential of metformin to prevent preterm delivery in women with polycystic ovary syndrome – an epi-analysis. Acta Obstet Gynecol Scand2012;91:1460–1464

Løvvik TS Carlsen SM Salvesen Ø et al.Use of metformin to treat pregnant women with polycystic ovary syndrome (PregMet2): a randomized, double-blind, placebo-controlled trial.Lancet Diabetes Endocrinol. 2019; (published online Feb 18.)

Ghazal Blair, Pharm.D. Candidate 2019, LECOM School of Pharmacy