Association of pregnancy outcomes in women with type 2 diabetes treated with metformin versus insulin when becoming pregnant

Abstract

Background: Metformin use in pregnancy is controversial because metformin crosses the placenta and the safety on the fetus has not been well-established. This retrospective study aimed to compare pregnancy outcomes in women with preexisting type 2 diabetes receiving metformin or standard insulin treatment. Methods: The cohort of this population-based study includes women of age 20-44 years with preexisting type 2 diabetes and singleton pregnancies in Taiwan between 2003 and 2014. Subjects were classified into three mutually exclusive groups according to glucose-lowering treatments received before and after becoming pregnant: insulin group, switching group (metformin to insulin), and metformin group. A generalized estimating equation model adjusted for patient age, duration of type 2 diabetes, hypertension, hyperlipidemia, retinopathy, and aspirin use was used to estimate the adjusted odds ratio (aOR) and 95% confidence interval (CI) of adverse pregnancy outcomes. Results: A total of 1166 pregnancies were identified in the insulin group (n = 222), the switching group (n = 318) and the metformin group (n = 626). The insulin group and the switching group had similar pregnancy outcomes for both the mother and fetus, including risk of primary cesarean section, pregnancy-related hypertension, preeclampsia, preterm birth (< 37 weeks), very preterm birth (< 32 weeks), low birth weight (< 2500 g), high birth weight (> 4000 g), large for gestational age, and congenital malformations. The metformin group had a lower risk of primary cesarean section (aOR = 0.57; 95% CI, 0.40-0.82) and congenital malformations (aOR, 0.51; 95% CI; 0.27-0.94) and similar risk for the other outcomes as compared with the insulin group. Conclusions: Metformin therapy was not associated with increased adverse pregnancy outcomes in women with type 2 diabetes as compared with standard insulin therapy.

Major malformations risk following early pregnancy exposure to metformin: a systematic review and meta-analysis

“…The selection process of studies fulfilling the inclusion criteria for the meta-analysis is shown in online supplemental figure 1. Out of 3783 records initially identified by database and trial register searching, a total of 11 studies were eventually included in the review and meta-analysis: two RCTs43 44 and nine observational studies 29 31 35 45–50. The details of included studies and characteristics of the studies participants are presented in tables 1 and 2.…”

“…We adopted a rigorous search strategy, and this meta-analysis is the most comprehensive and updated quantitative synthesis of the safety of metformin in terms of MCM after early pregnancy exposure. Since previous most recent meta-analysis, five additional studies were extracted and included for current meta-analysis 29 31 35 49 50. Out of these five studies, three had data on both PCOS and PGDM indications 29 31 35.…”

Comparación de factores y desenlaces entre diabetes gestacional y diabetes tipo 2 en México

“…En el grupo de metformina + insulina se detectaron más casos de muerte fetal. Se ha reportado en pacientes DMG menor presentación de desenlaces graves con metformina a diferencia de insulina, ya que en este último hubo desenlaces aumentados como cesáreas, preeclamsia, partos prematuros, muy prematuros y macrosomía 14 . Mientras que el grupo de metformina presentó menor incidencia de cesáreas y malformaciones congénitas y en general no estuvo asociado con otros desenlaces adversos.…”

Current Therapeutic Use of Metformin During Pregnancy: Maternal Changes, Postnatal Effects and Safety

“…A cohort was constructed including women of age 20 to 44 years with type 2 diabetes in Taiwan that had an insulin group, a metformin group, and a group that switched from metformin to insulin. It was concluded that the metformin group had a lower risk of primary cesarean section and congenital malformations while the insulin group and the group that switched to insulin had similar pregnancy outcomes between them that included risk of cesarean section, pregnancy-induced hypertension, and preterm birth [38]. Metformin has been stated to be under thorough assessment for its role as an adjuvant to cancer therapy [39].…”