499: Metformin and prediabetes: could early pregnancy metformin exposure decrease the risk of preeclampsia?

Abstract

Metformin has been found to have a role in promoting vascular remodeling and angiogenesis, which may reduce the risk of developing preeclampsia. Few studies have focused on pregnant women with prediabetes, however these women are at an increased risk for hypertensive disorders of pregnancy (HTN). We hypothesize metformin exposure decreases the risk of developing HTN in patients with prediabetes. Retrospective cohort study from 2009-2019 of singleton pregnancies complicated by prediabetes, defined as pre-pregnancy or first trimester hemoglobin A1c between 5.7 and 6.4%. We compared women who received metformin throughout pregnancy to those with no metformin exposure. Sensitivity analysis was performed for women who were taking metformin at conception or started in the first trimester. The primary outcome was a hypertension composite defined as gestational hypertension, preeclampsia with or without severe features, or HELLP syndrome. Individual hypertensive outcomes were also evaluated. Logistic regression was used adjust for confounding variables. Of 41,472 deliveries, 248 pregnancies were included. There was no difference in the primary outcome between women exposed and not exposed to metformin. Women exposed to metformin had a decreased risk of preeclampsia with severe features compared to those who were not exposed (aOR 0.32, 95% CI 0.11-0.95) (Fig 1). 52% of women receiving metformin were taking it at conception or started in the first trimester. The incidence of preeclampsia with severe features remained significantly less in women started on metformin in early pregnancy compared to non-exposed women (aOR 0.17, 95%CI 0.04-0.87) (Fig 2). Metformin exposure was associated with a decreased risk of preeclampsia with severe features in patients with prediabetes. These data suggest there may be benefit to metformin exposure beyond glycemic control, especially in the first trimester. This study also points to the importance of recognizing glucose intolerance early in pregnancy as patients with prediabetes have additional risk factors for obstetric complications.