Conflicting Studies Emerge on GLP-1 Receptor Agonists and Pregnancy Outcomes

New Haven, Connecticut – The use of glucagon-like peptide 1 receptor agonists (GLP-1 RA) such as semaglutide before or during pregnancy is under intense scrutiny following the Society for Maternal-Fetal Medicine (SMFM) 2025 Annual Pregnancy Meeting.Three studies presented at the meeting revealed contradictory findings regarding the impact of these medications on pregnancy outcomes, including preterm birth and hypertensive disorders. The research underscores the need for further investigation before any changes to current medical recommendations are considered. These studies examined preconception use of GLP-1 RAs and their effects on gestational weight gain, as well as the risk of hypertensive disorders.

The conflicting results from two cohort studies highlight the complexities of using GLP-1 RAs during pregnancy. Olga Grechukhina, MD, an assistant professor of OB/GYN at Yale School of Medicine, who was not involved in the studies, emphasized the need for a deeper understanding of these medications’ effects. She told Medscape Medical News that the discrepant results necessitate further research into the direct effects of these medications on placental function.

Dr. Grechukhina cautioned against the use of GLP-1 agonists during pregnancy until more robust safety data is available. In the absence of robust data to support the safety around the use of GLP-1 agonists in pregnancy and inconsistent but possible association with hypertensive disorders of pregnancy,this medication should continue to be halted during pregnancy, she stated.

Preconception Use of GLP-1s and Gestational Weight Gain

One of the studies focused on the use of GLP-1s prior to conception, although some participants continued the medication after becoming pregnant. Audrey Merriam, MD, MS, an associate professor of OB/GYN at Yale School of Medicine, introduced research led by Nishita Pondugula, MS, of Yale New Haven Hospital, which explored this area. Current evidence suggests similar rates of miscarriage, live birth, preterm delivery, gestational diabetes, hypertension in pregnancy, maternal weight gain, and neonatal birth weight between those with and without preconception exposure to GLP-1s.

Dr. Merriam noted that previous small observational human studies showed no increased risk of congenital malformations or adverse pregnancy outcomes after antepartum GLP-1 RA exposure. Given that patients frequently regain weight after stopping semaglutide, the researchers investigated potential differences in gestational weight gain among those who used GLP-1s up to a year before conception.

The retrospective cohort study analyzed pregnancies at their institution between 2014 and 2024,identifying 243 patients who used GLP-1 drugs up to one year before conception. These patients were prescribed GLP-1s for either pregestational diabetes or weight management. the study compared 103 patients taking GLP-1s for diabetes with 175 patients with pregestational diabetes who did not take GLP-1s. Additionally, 140 patients taking GLP-1s for obesity were compared with 200 patients not taking GLP-1s, including 100 with a body mass index (BMI) between 30 and 40 and 100 with a BMI ≥ 40. The matched cohorts were similar in age, proportion using public insurance, and proportion who were multiparous.

The majority of participants, 92%, had taken only one GLP-1 drug, with semaglutide being the most common at 63%. Other medications included liraglutide, dulaglutide, tirzepatide, and exenatide. On average, patients had taken their last dose of GLP-1 14 days before conception, with a median of 30 days after conception.

Researchers compared gestational weight gain between GLP-1-exposed and -unexposed patients, adjusting for baseline differences. In patients with pregestational diabetes, no critically important differences were found in weight gain compared to recommendations. However, among those with obesity, patients with GLP-1 exposure were considerably less likely to be below gestational weight gain recommendations (adjusted odds ratio [aOR], 0.38; 95% CI, 0.18-0.80).

Further stratification revealed that only those with postconception GLP-1 exposure were significantly less likely to gain less weight than recommended (aOR, 0.29; 95% CI, 0.12-0.72). Dr. Merriam suggested that the reduction in odds of being below recommended weight gain for those with postconception GLP-1 exposure may reflect nonpregnant findings showing rapid weight regain immediately after cessation.

Reduced Risk for Hypertensive Disorders?

A separate analysis by the same team, presented as a poster, examined the risk of hypertensive disorders of pregnancy in women who took GLP-1 medications in the year prior to conception. Pondugula and colleagues reported that preconception GLP-1 use halved the odds of developing a hypertensive disorder of pregnancy.

The analysis adjusted for baseline differences between groups. Among those with obesity, 37.5% of unexposed participants developed a hypertensive disorder of pregnancy, compared to 24% of those who had taken a GLP-1 (aOR, 0.5; P = .007). No significant differences were observed in either cohort for large for gestational age fetuses, fetal growth restriction, preterm birth, or fetal demise. Similarly, there were no significant differences between the exposed and unexposed obesity groups for gestational diabetes, insulin use, or metformin use.

The significant aORs remained only for those exposed after conception when comparing those with only preconception exposure to GLP-1s and those who continued taking GLP-1s after conception.

GLP-1 Exposure During Pregnancy: A Different Viewpoint

In contrast, a study by Emily N. Adams, MD, of Johns Hopkins School of Medicine, Baltimore, and colleagues, focused on GLP-1 exposure during pregnancy and its complications. This retrospective cohort study linked semaglutide to a lower risk of preterm birth but a higher risk of other pregnancy complications. Analyzing data from the Vizient Clinical Database, the researchers found that among 4,606,975 pregnant patients with type 2 diabetes, 0.2% (n = 9214) took semaglutide during pregnancy.

Patients taking semaglutide had a significantly lower incidence of preterm birth compared to those receiving standard care (aOR, 0.74; P < .001 after adjustment for maternal age, gestational age at study entry, obesity, pregestational diabetes, and chronic hypertension). Though pregnancies exposed to semaglutide had a greater risk preeclampsia, HELLP syndrome, and eclampsia, all P < .001 compared with unexposed pregnancies.

The authors emphasized the need for careful monitoring of patients exposed to semaglutide during pregnancy. our results underscore the need for careful monitoring of patients exposed to semaglutide in pregnancy, they wrote.

Contradictory Findings and the Need for Further research

Dr. Grechukhina expressed her initial reaction to the findings. I was not surprised to see that semaglutide exposure was associated with reduced risk of preterm birth, she told Medscape Medical News. I suspect that might be related to improved glycemic control, which in turn implies that fewer patients would require iatrogenic preterm birth for poorly controlled blood sugar.Interestingly, the study by Pondugula, et al did not find this association, which might perhaps be related to the lower number of participants.

However,she was surprised by the association between semaglutide exposure and increased risk for hypertensive disorders of pregnancy,as reported by Adams and colleagues,which contradicted the findings of Pondugala and colleagues. Dr. Grechukhina noted a limitation in the Adams study, stating that it is indeed unclear what counted as ‘exposure’ to semaglutide in relation to the onset of pregnancy.

The studies presented at the Society for Maternal-fetal Medicine (SMFM) 2025 Annual Pregnancy Meeting highlight the complexities and uncertainties surrounding the use of GLP-1 receptor agonists during pregnancy. While some findings suggest potential benefits, such as a reduced risk of preterm birth or hypertensive disorders, others indicate increased risks of pregnancy complications. The conflicting results underscore the urgent need for further research to fully understand the effects of these medications on both maternal and fetal health. until more conclusive data is available, caution and careful monitoring are advised for patients considering or using GLP-1 RAs during pregnancy.

GLP-1 Receptor Agonists & Pregnancy: A Risky Balancing Act? Expert weighs In

Are we risking potential harm to mothers and babies by prescribing glucagon-like peptide-1 receptor agonists (GLP-1 RAs) during pregnancy?

Interviewer: Dr. Anya Sharma, leading researcher in maternal-fetal medicine, welcome to World

GLP-1 Receptor Agonists & Pregnancy: A Risky Balancing Act? Expert weighs In

Are we risking potential harm to mothers and babies by prescribing glucagon-like peptide-1 receptor agonists (GLP-1 RAs) during pregnancy?

Interviewer: Dr. Anya Sharma,leading researcher in maternal-fetal medicine,welcome to World Today News. Recent studies on GLP-1 receptor agonists, like semaglutide, and their effects on pregnancy outcomes have presented conflicting results. Could you shed light on this complex issue for our readers?

Dr. Sharma: Thank you for having me. The use of GLP-1 receptor agonists during pregnancy is indeed a complex and evolving area. The conflicting data emerging from recent studies highlight the crucial need for more robust research before we can definitively understand the risks and benefits for both mother and child. Essentially, we’re navigating a delicate balancing act between managing maternal health conditions, like obesity and diabetes, and ensuring the safety of the pregnancy.

Interviewer: Several studies presented at the SMFM meeting showed contradictory findings regarding preterm birth and hypertensive disorders. Can you elaborate on these discrepancies?

Dr. Sharma: Yes, the discrepancies are significant. Some studies suggest a potential reduced risk of preterm birth with GLP-1 RA exposure,possibly due to improved glycemic control. However, other research has linked GLP-1 RA use, particularly semaglutide, to an increased risk of hypertensive disorders during pregnancy, like preeclampsia and HELLP syndrome. These contrasting results highlight the limitations of observational studies and the need for large-scale,well-designed randomized controlled trials to definitively establish causal relationships. The differing methodologies and study populations may also contribute to these conflicting findings. For instance, some studies focused on preconception use, while others looked at exposure during pregnancy.

Interviewer: What are the key factors contributing to the uncertainty surrounding the use of GLP-1 RAs during pregnancy?

Dr. Sharma: several factors contribute to the current uncertainty. These include:

Limited data: We simply don’t have enough high-quality data from large,well-designed studies to fully assess the long-term effects of GLP-1 RAs on pregnancy outcomes.

Confounding factors: Many factors influence pregnancy outcomes, making it challenging to isolate the specific effects of GLP-1 RAs.This includes pre-existing conditions, lifestyle factors, and other medications the mother might potentially be taking.

Variability in drug exposure: The dose, timing, and duration of GLP-1 RA exposure may significantly impact the outcome.

Timing of exposure: Evaluating the impact of preconception versus during-pregnancy exposure.

Dosage: Determining whether dose affects pregnancy outcomes,particularly if a reduced dose could mitigate risk.

Specific GLP-1 RAs: Investigating variations in effects across different GLP-1 RA medications.

Interviewer: Thank you,Dr. Sharma, for your expert insights. This nuanced discussion highlights the importance of ongoing research and careful clinical decision-making.

Final Thought: The conflicting data surrounding GLP-1 RAs and pregnancy underscores the need for further research. Healthcare professionals and expectant mothers should engage in open conversations to weigh the potential risks and benefits before making any decisions. What are your thoughts? Share your comments below!