Perinatal outcomes associated with metformin use during pregnancy among women with pregestational type 2 diabetes mellitus

Objective: We emulated a modified randomized trial (MiTy) to compare the perinatal outcomes among those continuing versus discontinuing metformin during pregnancy for women with type 2 diabetes treated with metformin plus insulin before pregnancy.

Research Design and Methods: This study used two healthcare claims databases (United States, 2000-2020). Pregnant women aged 18-45 years with type 2 diabetes who were treated with metformin plus insulin at conception were eligible. The primary outcome was a composite of preterm birth, birth injury, neonatal respiratory distress, neonatal hypoglycemia, or neonatal intensive care unit admission. Secondary outcomes included the components of the primary composite outcome, gestational hypertension, preeclampsia, maternal hypoglycemia, cesarean delivery, large-for-gestational-age infants, small-for-gestational-age infants (SGA), sepsis, and hyperbilirubinemia. We adjusted for potential baseline confounders including demographic characteristics, comorbidities, and proxies for diabetes progression.

Results: Of 2,983 eligible patients, 72% discontinued use of metformin during pregnancy. The average age at conception was 32 years and the prevalence of several comorbidities was higher among continuers. The risk of the composite outcome was 46% for continuers and 48% for discontinuers. The adjusted risk ratio was 0.92 (95% CI: 0.81, 1.03). Risks were similar between treatments and consistent between databases for most secondary outcomes except for SGA, which was elevated among continuers only in the commercially insured population.

Conclusions: Our findings were consistent with those reported in the MiTy randomized trial. Continuing metformin during pregnancy was not associated with increased risk of a neonatal composite adverse outcome. However, a possible metformin-associated risk of SGA warrants further consideration.