TL;DR
Two systematic reviews found no clear increase in most measured adverse pregnancy outcomes among women exposed to GLP-1 drugs around conception or early pregnancy. The researchers caution that the evidence is limited and does not support using the drugs during pregnancy; current advice to stop before planned conception remains in place.
Two systematic reviews found no clear increase in most measured adverse pregnancy outcomes among women who used GLP-1 receptor agonists around conception or early pregnancy. Researchers said the findings do not establish that the drugs are safe during pregnancy. The studies examined outcomes after inadvertent exposure; current advice to stop treatment before planned conception remains unchanged.
One review, published in Med, pooled results from 10 studies covering more than 2.1 million pregnancies. It found no clearly detectable rise in miscarriage or intrauterine death, congenital anomalies, preterm birth, hypertensive disorders, gestational diabetes, abnormal fetal growth or excess gestational weight gain among women exposed during the periconceptional period compared with those who were not exposed.
The analysis found a lower pooled estimate for preeclampsia among exposed women: an odds ratio of 0.87, with a 95% confidence interval of 0.78 to 0.98. That result came from only two datasets. Asma Khalil, MD, MSc, of City St George’s University of London, and colleagues said it should be interpreted cautiously and does not show that the drugs prevent preeclampsia.
A second review, presented at the European Association for the Study of Diabetes annual meeting and published in Lancet Obstetrics, Gynaecology, & Women’s Health, included data on more than 40,000 women, primarily with type 2 diabetes. Across four studies, stopping GLP-1 drugs during the first trimester was not associated with a rise in congenital anomalies (risk ratio 1.02; 95% CI 0.96 to 1.08). Across two studies, early pregnancy loss was more common among exposed women (RR 1.31; 95% CI 1.26 to 1.35), but the researchers said the result was difficult to interpret because the largest study combined miscarriage and termination.
Guidance Still Favors Stopping Before Conception
GLP-1 medicines are used for diabetes and other indications, and exposure can occur before a pregnancy is recognized. The first review’s authors said the results may provide limited reassurance after inadvertent exposure before conception or early in pregnancy. They said the findings do not support continued treatment during pregnancy.
GLP-1 drugs are not approved for use during pregnancy. Their labeling advises stopping at least two months before a planned conception, although that guidance is based on limited human data. The reviews do not provide grounds to change that recommendation. Tricia Tan, MBChB, PhD, of Imperial College London, said the studies found no detectable serious problem in the outcomes examined and noted that studies of past practice may not reflect current practice.
The second review’s authors also developed an international consensus statement on GLP-1 use before, during and after pregnancy for women with diabetes. Claire Meek, PhD, of the University of Leicester, said the guidance sets clinical targets for preconception use and calls for strategies to help women understand when and how to stop treatment safely. She said contraception remains strongly recommended while taking GLP-1 drugs, and treatment should stop in early pregnancy if conception occurs.
Evidence Spans Different Pregnancy Questions
The two reviews address related but distinct questions. The analysis published in Med considered a range of maternal and perinatal outcomes after exposure around conception. The EASD review focused on evidence that included women with diabetes and examined outcomes such as congenital anomalies after treatment was stopped during the first trimester. Their similar findings on many outcomes do not remove the limits of the underlying data.
Khalil and colleagues cited varying definitions of exposure, possible residual confounding and few studies for several outcomes. The EASD consensus authors said evidence is particularly scarce for use in type 1 diabetes, despite interest among women with the condition. They also discussed possible use before conception and after birth for people with gestational diabetes, while noting a lack of direct evidence. Data on GLP-1 drugs during lactation remain limited; the consensus statement advised breastfeeding women who use them to stay at the lowest effective dose.
“The findings “may provide limited reassurance following inadvertent exposure before conception or during early pregnancy, but they should not be interpreted as supporting continued treatment during pregnancy.””
— Asma Khalil, MD, MSc, and colleagues
Safety Questions Remain Open
The reviews cannot rule out risks that the available studies were too limited to detect. Researchers said evidence was weaker for some outcomes because few studies contributed, and differences in how exposure was defined make results harder to compare. The preeclampsia estimate rests on two datasets, while the early pregnancy loss result is hard to separate into miscarriage and termination based on the largest contributing study.
The studies also do not establish how risks may differ by drug, dose, duration of use or timing of exposure. Nor do they settle questions about use in type 1 diabetes, gestational diabetes or while breastfeeding. The researchers said more robust evidence is needed; no new safety clearance for pregnancy use was reported.
Researchers Seek Better Pregnancy Data
For now, the review authors said recommendations to discontinue GLP-1 receptor agonists before planned conception should remain unchanged. Meek’s consensus statement calls for practical guidance to help women plan when to stop and how to do so safely, alongside contraception during treatment and stopping if pregnancy occurs.
The authors also called for greater investment in women’s health research, regulatory changes that permit evidence generation while maintaining safety, and mandatory reporting of sex-disaggregated data. Further studies will be needed to clarify outcomes across different drugs, indications and stages of pregnancy, as well as during lactation.
Key Questions
Do these studies show that GLP-1 drugs are safe during pregnancy?
No. The reviews found no clear increase in most measured outcomes, but their authors said the evidence is limited and does not establish safety or support continued treatment during pregnancy.
What should someone do before a planned pregnancy?
Drug labeling advises stopping GLP-1 receptor agonists at least two months before planned conception. The researchers said current recommendations should remain unchanged; people should discuss medication decisions with their clinician.
What did the second review find about early pregnancy loss?
It reported a higher rate of early pregnancy loss among exposed women across two studies (RR 1.31; 95% CI 1.26 to 1.35). The researchers said the result was difficult to interpret because the largest contributing study combined miscarriage and termination.
Is there enough evidence about GLP-1 drugs during breastfeeding?
No. The source report says data on lactation remain scarce. The consensus statement advised women using these drugs while breastfeeding to use the lowest effective dose.
Source: rss
