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

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Two systematic reviews found no clearly detectable increase in most measured adverse pregnancy outcomes after GLP-1 drug exposure around conception or early pregnancy. The researchers said the findings do not establish safety. Review authors said recommendations to discontinue treatment before planned conception should remain unchanged.

Two systematic reviews found no clearly detectable rise in most measured adverse pregnancy outcomes among women exposed to GLP-1 receptor agonists around conception or early pregnancy, but researchers said the findings do not establish that the drugs are safe during pregnancy. The evidence offers limited reassurance after inadvertent exposure, while current recommendations to stop the medicines before planned conception should remain unchanged.

One systematic review and meta-analysis covered 10 studies and more than 2.1 million pregnancies. Compared with women who had not used GLP-1 drugs in the periconceptional period, the pooled results showed no clear increase in miscarriage or intrauterine death, congenital anomalies, preterm birth, hypertensive disorders, gestational diabetes, small- or large-for-gestational age, or excess gestational weight gain.

The analysis found a lower pooled estimate for preeclampsia, with an odds ratio of 0.87 and a 95% confidence interval of 0.78 to 0.98. That result came from only two datasets. Lead author Asma Khalil and colleagues said it should be interpreted cautiously, and emphasized that the review could not establish safety because of differences in how exposure was defined, possible residual confounding, and the small number of studies contributing to several outcomes.

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. It found no increase in congenital anomaly risk when GLP-1 drugs were discontinued during the first trimester: the pooled risk ratio was 1.02, with a 95% confidence interval of 0.96 to 1.08 across four studies. Early pregnancy loss was more common in the exposed group in two studies, but the researchers said interpretation was difficult because the largest study combined miscarriage and termination.

Pregnancy Decisions Still Need Caution

The reviews assessed outcomes associated with GLP-1 exposure around conception and in early pregnancy. The drug class is expanding in popularity and indications, according to the report. The reviews detected no clear increase in most measured outcomes, but they do not show that continuing treatment during pregnancy is safe or beneficial. An absence of a clearly detected increase in these studies does not establish that there is no risk.

GLP-1 drugs are not approved for use during pregnancy. Product labeling recommends stopping them at least two months before a planned conception, although the report notes that this guidance rests on limited human data. The reviews do not provide grounds to change that advice. People taking one of these medicines who are planning a pregnancy or discover they are pregnant should discuss treatment decisions with a qualified clinician.

The authors of the second review also developed a consensus statement on using GLP-1 drugs before, during, and after pregnancy for women with diabetes. They called for clinical strategies to help women understand when and how to stop treatment, and said contraception is strongly recommended during use. The statement offers clinical targets and suggested strategies, but does not add direct evidence on pregnancy safety.

What the Two Reviews Examined

The first review combined evidence from studies of GLP-1 exposure around conception and compared outcomes among women who used GLP-1 drugs in the periconceptional period with outcomes among those who did not. Its authors reported that subgroup analyses by the reason for treatment were consistent with the main findings. The studies differed in their definitions of exposure, and a small number of studies contributed to several outcomes.

The second review focused on a separate body of evidence, largely involving women with type 2 diabetes. Claire Meek of the University of Leicester and colleagues said their analysis informed an international consensus statement. They also noted that there is almost no evidence for GLP-1 use in type 1 diabetes, data remain scarce regarding lactation, and direct evidence in gestational diabetes is lacking.

Tricia Tan of Imperial College London, commenting through the U.K.’s Science Media Centre, said the reviews found no detectable serious problem across the pregnancy outcomes examined. She cautioned that studies of past practice may not reflect current use. This limits what the evidence can say as prescribing patterns and the number of people exposed around pregnancy change.

“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

Limits in the Pregnancy Evidence

The reviews do not establish that GLP-1 drugs are safe during pregnancy. The evidence is limited by variation in exposure definitions, potential residual confounding, and relatively few studies for several outcomes. The report does not provide enough evidence to determine whether the reported findings differ by specific GLP-1 drug, dose, length of use, or timing of exposure.

The early pregnancy loss finding in the second review remains difficult to interpret: its pooled risk ratio was 1.31, with a 95% confidence interval of 1.26 to 1.35 across two studies, but the largest contributing study combined miscarriage with termination. The preeclampsia estimate in the first review also came from only two datasets.

Evidence is scarce on use in type 1 diabetes, gestational diabetes, and while breastfeeding. Tan cautioned that studies of past practice may not reflect current use. No study finding described here supports continued GLP-1 treatment during pregnancy.

Guidance and Research to Follow

For now, the authors say the recommendation to stop GLP-1 receptor agonists at least two months before planned conception should remain in place; the medicines are not approved for use during pregnancy. Meek said contraception remains strongly recommended while taking the drugs and that treatment should stop in early pregnancy if conception occurs.

The consensus statement calls for clinical strategies that help women understand when and how to discontinue treatment safely, as well as more investment in women’s health research. Meek and colleagues also called for regulatory changes that permit evidence generation while protecting women and unborn children, and for mandatory reporting of sex-disaggregated data. The authors called for more robust evidence.

Key Questions

Do these studies prove 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. They do not support continuing treatment during pregnancy.

What should someone do if they become pregnant while taking a GLP-1 drug?

The report says treatment should stop in early pregnancy if conception occurs, and that people should seek guidance from their clinician about their care. The studies do not provide a basis for making individual treatment decisions without medical advice.

How long before a planned pregnancy should GLP-1 treatment be stopped?

Drug labeling recommends stopping GLP-1 receptor agonists at least two months before planned conception. The review authors said current recommendations should remain unchanged while stronger evidence is awaited.

Did the second review find a higher risk of early pregnancy loss?

It reported a higher pooled rate of early pregnancy loss among exposed women across two studies, with a risk ratio of 1.31. However, the researchers said the result is difficult to interpret because the largest study combined miscarriage and termination.

Is there enough evidence about GLP-1 drugs and breastfeeding?

No. The report describes data on lactation as scarce. The consensus authors advised that women using these medicines while breastfeeding stick to the lowest effective dose, but the available evidence remains limited.

Source: rss