Risk Factors and Pregnancy Outcomes Associated with Insulin Addition to Metformin Therapy in Gestational Diabetes

Metformin is increasingly being used to treat gestational diabetes mellitus (GDM). But pharmacotherapy with metformin frequently requires insulin supplementation to achieve glucose control, and this remains poorly characterized. We identified factors associated with insulin supplementation of metformin versus receipt of metformin alone, and then examined whether these two groups differed in the frequency of adverse pregnancy outcomes (APOs) among individuals with GDM.We conducted a retrospective analysis of a U.S. GDM care program from 2018 to 2021, which first initiated metformin.Modified Poisson regression was used to identify risk factors associated with later insulin supplementation after initial metformin treatment, and stepwise regression was used to identify the most predictive factors. A propensity matched analysis was used to examine the association between metformin with insulin supplementation versus metformin alone (reference) with APOs (hypertensive disorders of pregnancy [HDP], preterm birth [PTB], small for gestational age [SGA], large for gestational age [LGA], and neonatal intensive care unit [NICU] admission).Among 399 deliveries with GDM that initiated metformin, 28.8% required insulin supplementation. Factors associated with an increased risk of insulin supplementation were older age, private insurance, and a higher mean screening glucose tolerance test; factors associated with a decreased risk were later GDM diagnosis and Black and Hispanic race and ethnicity. Individuals who required metformin with insulin supplementation had a higher risk of LGA birth (28.6 vs. 13.9%; adjusted risk ratio [aRR]: 1.89; 95% CI: 1.18, 3.02) and NICU admission (25.8 vs. 13.5%; aRR: 1.79; 95% CI: 1.11, 2.88).Multiple patient characteristics were associated with insulin supplementation after starting metformin to treat GDM. Pregnant individuals with GDM who required insulin supplementation of metformin had a higher risk of LGA and NICU admission. · Multiple patient characteristics were associated with insulin supplementation of metformin for GDM.. · Individuals treated with insulin supplementation of metformin had a higher risk of LGA and NICU admission versus those treated with metformin alone.. · Data about whether identification of individuals who require metformin supplementation with insulin results in improved outcomes are needed..