Metformin and risk of adverse pregnancy outcomes among pregnant women with gestational diabetes in the United Kingdom: A population-based cohort study

Aims: Metformin is increasingly used off-label as the treatment of gestational diabetes (GDM). Our objective was to determine if metformin versus insulin initiation is associated with the adverse pregnancy outcomes.

Materials and methods: We conducted a retrospective cohort study using data from the Clinical Practice Research Datalink, its pregnancy register, and Hospital Episode Statistics from 1998 to 2018. We included pregnancies of women who initiated metformin or insulin between 20 weeks gestation and pregnancy end. The primary outcome was a composite outcome of large for gestational age (LGA) and macrosomia. The secondary outcomes included small for gestational age (SGA), preterm birth, caesarean delivery, and hypertensive disorders during pregnancy (HDP). Inverse probability weighted-Cox proportional hazards models were to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CI), comparing those who initiated metformin versus insulin at cohort entry, accounting for baseline covariates.

Results: Our cohort included pregnancies of 1297 women initiating metformin and of 895 women initiating insulin. Compared to insulin initiation, metformin initiation was associated with a decreased risk of LGA or macrosomia (HR 0.64, 95% CI 0.49, 0.78), Caesarean delivery (HR 0.83, 95% CI 0.69, 0.98), and preterm birth (HR 0.83, 95% CI 0.58, 1.08). The HRs for HDP and SGA were 0.92 (95% CI 0.57, 1.27) and 1.33 (95% CI 0.67, 2.00), respectively.

Conclusions: Our study suggests that, compared to initiating insulin, initiating metformin is associated with decreased risks of adverse pregnancy outcomes among women with GDM. These findings provide important real-world evidence regarding the use of metformin for GDM.