Prepregnancy GLP-1 receptor agonist use linked to increased gestational weight gain

medwireNews: Women prescribed glucagon-like peptide (GLP)-1 receptor agonists up to 3 years before pregnancy experience greater gestational weight gain following discontinuation than those not exposed to the treatment, US research shows. 

“These findings are consistent with those of prior studies that observed weight regain after discontinuation of GLP-1 [receptor agonist] therapy outside pregnancy and may guide obstetric risk assessment for women who discontinue GLP-1 [receptor agonists] for pregnancy,” write Jacqueline Maya (Harvard Medical School, Boston, Massachusetts) and co-authors in JAMA. 

They studied data for 448 women with singleton pregnancies between 2016 and 2025 who had at least one prescription for a GLP-1 receptor agonist between 3 years before and 90 days after conception. More than half (58%) had a treatment duration of less than 6 months, and two thirds had their last GLP-1 receptor agonist order within 6 months of conception. 

The women had a mean age of 34.0 years and a prepregnancy BMI of 36.1 kg/m2; 84% had obesity and 23% had pre-existing diabetes. They were matched for clinical and social factors to 1344 women who had not used a GLP-1 receptor agonist before or during pregnancy. 

Maya et al report that women with a history of GLP-1 receptor agonist use had significantly greater mean gestational weight gain than their unexposed counterparts, at 13.7 kg versus 10.5 kg. 

Compared with the unexposed group, the GLP-1 receptor agonist-exposed group also had significantly higher rates of excess gestational weight gain according to 2009 Institute of Medicine guidelines thresholds (65 vs 49%), preterm delivery (17 vs 13%), gestational diabetes (20 vs 15%), and hypertensive disorders of pregnancy (46 vs 36%), as well as babies with a higher mean birthweight percentile for gestational age (58.4 vs 54.8%). 

Conversely, there was no difference between the two groups in birth length, or in the risks for cesarean delivery, or for having newborns with large or small for gestational age birthweight. 

The investigators observed similar results when they stratified the participants by pre-existing type 2 diabetes status and restricted the analysis to recent (6 months before to 90 days after conception) GLP-1 receptor agonist users. And they note that there was a trend toward lower gestational weight gain with liraglutide than with semaglutide (12.7 vs 14.4 kg), but the difference did not reach statistical significance. 

One limitation of the research, say the authors, is the fact that participants were matched by prepregnancy BMI rather than BMI before GLP-1 receptor agonist treatment, meaning the analysis could not determine the potential benefits of initiating GLP-1 receptor agonist therapy with the aim of entering pregnancy at a lower weight. 

In an accompanying comment, Carolyn Cesta (Karolinska Institutet, Stockholm, Sweden) and co-authors say that this omission means that although the results “provide valuable answers to questions about prior GLP-1 [receptor agonist] use as an obstetric risk factor, [they] do not provide direct evidence to inform clinical counseling before initiation of GLP-1 [receptor agonist] treatment about its potential harms and benefits for future pregnancies.” 

Cesta et al continue: “The absence of evidence on this latter question is likely due to the paucity of data on BMI before GLP-1 [receptor agonist] treatment in real-world databases and the substantial effort required to link these data to prescription and pregnancy records.  

“Yet with the rapid uptake of GLP-1 [receptor agonist] and newer pharmaceutical weight-loss agents and the desire to harness their potential to improve pregnancy outcomes in women with obesity, it is critical that we strive to generate the evidence needed both to inform obstetric care and guide treatment initiation decisions.” 

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2025 Springer Healthcare Ltd, part of Springer Nature 

JAMA 2025; doi:10.1001/jama.2025.20951 
JAMA 2025; doi:10.1001/jama.2025.19841