Continuation of glucagon-like peptide-1 receptor agonists during the first trimester of pregnancy may not associated with a clear increase in nonlive birth, abnormal fetal growth, or major congenital malformations in a recent study.
In a target trial emulation study, investigators used Merative MarketScan commercial insurance claims data from 2011 to 2024. They included 3,572 pregnancies among patients aged 16 to 55 years who received a glucagon-like peptide (GLP)-1 receptor agonist prescription in the 90 days prior to their last menstrual period. The investigators compared primary outcomes, including nonlive birth, small for gestational age, large for gestational age, and nonchromosomal major congenital malformations among pregnant women who continued treatment into the first trimester and those who did not continue treatment following conception.
Among all pregnancies, the investigators estimated about a 30% risk of nonlive birth among patients who continued treatment compared with 27% among those who did not. The adjusted risk ratio of 1.09 was found to be most compatible with either no difference or a small difference in risk.
Of 2,529 live-birth pregnancies, 57% of the pregnant patients received at least one GLP-1 receptor agonist prescription following the last menstrual period. The investigators linked 1,499 pregnancies to infants with sufficient follow-up to evaluate neonatal outcomes.
The investigators did not identify a clear increase in fetal growth abnormalities or major congenital malformations among the patients who continued GLP-1 receptor agonists. Major congenital malformations were identified in about 8% of infants exposed to continued treatment and 7% of infants in the noncontinuation group. The prevalence of small for gestational age and large for gestational age birth was also comparable between groups.
Elective termination occurred more frequently among the pregnant patients who continued treatment into pregnancy. The investigators noted that differences in pregnancy intention, pregnancy recognition, concerns about drug exposure, and other factors may have contributed to this finding. Rates of spontaneous abortion were similar between groups.
The results were generally consistent in analyses stratified by type 2 diabetes status and across multiple sensitivity analyses.
The investigators noted several limitations. The observational design leaves the possibility of residual confounding, particularly related to glycemic control, which could not be fully measured in claims data. Most patients classified as continuers received only one additional prescription following conception, limiting assessment of prolonged exposure later in pregnancy. The study also could not evaluate pregnancy losses occurring prior to clinical recognition. In addition, estimates for major congenital malformations and small for gestational age remained imprecise because of the relatively small number of events. The investigators concluded that the findings do not indicate a strong association between first-trimester GLP-1 receptor agonist continuation and adverse pregnancy outcomes, although uncertainty remains for less common outcomes.
"There was no indication of a strong effect of GLP-1 [receptor agonist] continuation into the first trimester on nonlive birth, [small for gestational age], [large for gestational age], or [major congenital malformation]," wrote lead study author Jeremy P. Brown, PhD, of the Department of Epidemiology at the Harvard T. H. Chan School of Public Health as well as the Faculty of Life Sciences & Medicine at King’s College London, and colleagues.
The study was funded by the National Institute of Child Health and Human Development. Full disclosures of the study authors can be found in the study.
Source: Annals of Internal Medicine
