Background: Metformin is recommended for treatment of type 2 diabetes among non-pregnant individuals. Although oral hypoglycemic agents such as metformin have gained acceptance for the treatment of gestational diabetes, insulin is the recommended first-line treatment for pregnant individuals with type 2 diabetes. The added benefit of metformin in pregnancies complicated by insulin-treated type 2 diabetes is unknown.
Objective: Thus, the objective of this trial was to compare the safety and efficacy of insulin plus metformin versus insulin alone for the treatment of type 2 diabetes in pregnancy.
Study Design: This was a multicenter, randomized, double-blind trial of individuals with insulin-treated type 2 diabetes (known diagnosis prior to pregnancy or diagnosed at <20 6/7 weeks’ gestation) who were carrying a singleton gestation with no known fetal anomalies. Enrolled participants were given metformin (or matching placebo) and instructed to take 500mg twice daily for 1 week followed by 1000mg twice daily until delivery. Insulin was titrated at the discretion of the obstetric provider to achieve glycemic control. The primary outcome was an adverse neonatal composite of neonatal hypoglycemia, birth trauma, hyperbilirubinemia, preterm delivery <37 weeks’ gestation, large-for-gestational-age, small-for-gestational-age, or fetal or neonatal death. Key secondary outcomes included neonatal anthropometrics and maternal hypoglycemia.
Results: Of 2,667 screened individuals at 18 centers, 831 were enrolled and randomized. Overall, the mean maternal age at enrollment was 33 ± 6 years. The cohort was racially diverse with 41% participants who self-identified as White, 30% Black or African American, 3% Asian, 1% mixed, and 24% not reported. Approximately 50% were of Hispanic ethnicity. The majority (77%) had diabetes diagnosed prior to pregnancy. The mean gestational age at birth was 37 ± 2 weeks’ gestation with preterm birth in 31% of participants. Overall, the mean birthweight was 3164 ± 768g with equal distribution of male and female neonates.