No Clear Risks With GLP-1s Around Pregnancy, but Caution Urged

Use of GLP-1 receptor agonists around pregnancy did not appear to increase adverse maternal or perinatal outcomes, according to two studies.

In a systematic review and meta-analysis of 10 studies representing over 2.1 million pregnancies published in Med, pooled estimates showed no clearly detectable increase in the following adverse outcomes among women who used GLP-1 drugs in the periconceptional period compared with those who did not:

• Miscarriage or intrauterine death
• Congenital anomalies
• Preterm birth
• Hypertensive disorders of pregnancy
• Gestational diabetes
• Small-for-gestational age or fetal growth restriction
• Large-for-gestational age
• Excess gestational weight gain

There was also a lower pooled estimate for preeclampsia (OR 0.87, 95% CI 0.78-0.98, P=0.02), but this was based on two datasets and “should be interpreted cautiously,” noted Asma Khalil, MD, MSc, of City St George’s University of London, and colleagues.

Subgroup analyses by drug indication yielded findings consistent with the primary analysis.

The results “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,” the authors wrote. “Until more robust evidence is available, current recommendations to discontinue GLP-1 receptor agonists before conception should remain unchanged.”

Khalil and team emphasized that the findings do not establish safety, as the evidence remains limited by exposure-definition heterogeneity, residual confounding, and the small number of studies contributing to several outcomes.

GLP-1 drugs are not currently approved for use during pregnancy. Drug labeling recommends stopping them at least 2 months prior to planned conception, though this guidance relies on limited human data. With the blockbuster drug class expanding in popularity and indications, inadvertent periconception and early-pregnancy exposure has likely risen, Khalil and colleagues noted.

“The message is broadly reassuring in that there was no detectable serious problem for pregnancy outcomes,” said Tricia Tan, MBChB, PhD, of Imperial College London, in comments posted to the U.K.’s Science Media Centre website.

However, “such studies are always limited by the fact that they are looking at past practice, which may not reflect current practice,” she added.

A second systematic review and meta-analysis — presented at the European Association for the Study of Diabetes (EASD) annual meeting and published in Lancet Obstetrics, Gynaecology, & Women’s Health — reached similar conclusions.

In this study, which included data on over 40,000 women who primarily had type 2 diabetes, no increase in congenital anomaly risk was observed when GLP-1 drugs were discontinued during the first trimester (risk ratio [RR] 1.02, 95% CI 0.96-1.08 across four studies), reported Claire Meek, PhD, of the University of Leicester in England, and colleagues.

However, early pregnancy loss (under 14-22 weeks), including miscarriage or termination, was more common among women exposed to GLP-1 drugs compared with those unexposed (RR 1.31, 95% CI 1.26-1.35 across two studies), though the researchers noted that this finding was difficult to interpret because miscarriage and termination were combined in the largest contributing study.

GLP-1 drug use was not associated with any other safety or efficacy outcomes.

Following the meta-analysis, the authors crafted the first international consensus statement for the use of GLP-1 drugs before, during, and after pregnancy in women with diabetes.

“We’ve given new targets for what we should be looking for clinically if we are using them preconception, and we have suggested that strategies are needed to help women understand when to come off these and how to do so safely,” Meek said at the EASD meeting.

She stressed that contraception remains “strongly recommended” while taking GLP-1 drugs, and treatment should stop in early pregnancy if conception occurs.

Addressing the drugs’ potential use in type 1 diabetes, she noted that there is “a lot of interest from women but almost no evidence.” The consensus statement acknowledged that GLP-1 drugs may offer benefits for these patients and outlined safe prescribing guidance. Similarly, despite a lack of direct evidence in gestational diabetes, Meek and colleagues suggested that GLP-1 drugs could prove beneficial in the preconception period and postnatally, recommending up to 12 months of use.

Data remain scarce regarding lactation. Meek and team advised women using GLP-1 drugs while breastfeeding to stick to the lowest effective dose.

“We call for a step-change in greater investment in women’s health research,” said Meek. “We call for regulatory change that enables evidence generation while maintaining safety of women and their unborn children. We also stand for mandatory reporting of sex-disaggregated data so that future studies can make greater progress in this area.”