[R01] Evaluating the safety and efficacy of glucagon-like peptide-1 receptor agonists for pre-pregnancy weight management and improved pregnancy outcomes
Ente: Eunice Kennedy Shriver National Institute of Child Health and Human Development
Scadenza: 2031-06-30
Importo max: $785,385
Paese: US
Descrizione
Summary
Women who are obese at pregnancy onset have a high likelihood for adverse outcomes during pregnancy,
including spontaneous abortion, gestational diabetes (GDM), hypertensive disorders, cesarean delivery, and
preterm birth, as well as cardiovascular and metabolic conditions post-pregnancy. Offspring of mothers who
are obese are also at increased risk of outcomes such as large for gestational age (LGA), malformations,
metabolic disorders. Healthy weight loss before pregnancy is recommended to reduce risks related to obesity.
Additionally, weight loss attempts are common among women with obesity who are planning to become
pregnant. Of prevailing weight loss treatments, long-acting glucagon-like peptide-1 receptor agonists (GLP-
1RA) (semaglutide, liraglutide) and related therapies (tirzepatide) have recently emerged as popular and
effective treatments for both diabetes and obesity. However, despite widespread use, little is known about
GLP-1RA use prior to or during pregnancy. We will leverage the National Patient Centered Clinical Research
Network (PCORnet) to identify a retrospective electronic health record (EHR)-based cohort of women with
pregnancies and their infants to address important knowledge gaps related to GLP-1RA use and pregnancy
outcomes. We hypothesize that GLP-1RA use prior to pregnancy, by virtue of reducing pre-pregnancy obesity,
will reduce risks of obesity-related pregnancy outcomes, including (but not limited to) gestational diabetes and
hypertensive disorders of pregnancy. However, under the premise that discontinuation of GLP-1RAs has been
shown to promptly initiate rebound weight gain in clinical trials, we also hypothesize that pre-pregnancy GLP-
1RA use (and discontinuation prior to or early in pregnancy) will result in higher GWG than other less effective
anti-obesity medications. Finally, as animal models suggest potential risks to the developing fetus, we
hypothesize that GLP-1RA use in early pregnancy will be associated with fetal/neonatal outcomes such as
stillbirth, malformations and NICU admission. The use of PCORnet will facilitate the identification and
longitudinal follow-up of a multi-center cohort of women and their infants, including weight/BMI, medication
prescribing, encounters (including diagnoses and procedures), and laboratory results, thereby providing
concrete and novel advantages over existing studies of GLP-1RAs and pregnancy to date. By asking
innovative questions around GLP-1RAs and pregnancy, we will help inform new clinical guidelines for GLP-
1RA use among women who are pregnant or planning to become pregnant.
Istituzione: VANDERBILT UNIVERSITY MEDICAL CENTER
PI: Margaret A. Adgent
Progetto: 1R01HD120349-01A1
Settori: Eunice Kennedy Shriver National Institute of Child Health and Human Development
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