As GLP-1 drugs have become more widely used for diabetes and weight management, an important question has followed: What happens if someone becomes pregnant while taking one?
A new systematic review and meta-analysis offers some reassurance, especially for women who were exposed around conception or early in pregnancy and then stopped taking the medication. Researchers found no increased risk of congenital anomalies, or birth defects, compared with pregnancies without GLP-1 exposure.
But the evidence is still far from complete. Most of the available research looks at exposure before pregnancy or during the first trimester, and the overall quality of the evidence was rated very low. There is still little information about use later in pregnancy, during breastfeeding or about long-term outcomes for children.
The review, published in The Lancet Obstetrics, Gynaecology & Women’s Health, included 23 studies overall, with seven used in the meta-analysis. Most of the women had type 2 diabetes.
GLP-1-based medications can improve blood sugar control and promote weight loss, which may be helpful before pregnancy for women trying to improve their metabolic health. But these drugs are not approved for use during pregnancy, and current guidance generally recommends stopping them before conception.
Still, unplanned pregnancies happen, and more women of reproductive age are now taking these medications.
That makes early-pregnancy safety a growing concern.
Across four studies involving more than 42,000 exposed pregnancies, researchers found no significant increase in birth defects after GLP-1 exposure around conception or early pregnancy.
They also found no significant differences in several other outcomes, including preterm birth, stillbirth or neonatal death, cesarean delivery, pregnancy-related high blood pressure disorders and babies born small for gestational age.
Those findings are encouraging, but they do not prove the drugs are safe during pregnancy.
Much of the research was observational, meaning researchers looked back at what happened rather than testing the medications under controlled conditions. Many studies also had limitations in how well they accounted for factors such as body weight, blood sugar control and severity of diabetes, all of which can affect pregnancy outcomes.
The most difficult result to interpret involved early pregnancy loss.
In the pooled analysis, women exposed to GLP-1 drugs appeared to have a 31% higher rate of early pregnancy loss. But the largest study grouped miscarriages and elective terminations together, making it impossible to know whether miscarriage itself was actually more common.
That uncertainty is one reason the authors say the current evidence should be interpreted cautiously.
There are even bigger gaps later in pregnancy.
Very few studies included women who continued taking GLP-1 drugs into the second or third trimester. Evidence during breastfeeding is also limited. Two small studies found little or no measurable semaglutide or tirzepatide in breast milk, but there is not enough clinical data to know whether these medications are safe for breastfeeding infants.
The review also highlights a practical challenge for women with diabetes who are planning a pregnancy.
Improving blood sugar control and, when needed, losing weight before conception can help reduce pregnancy risks. GLP-1 drugs may help with both. But stopping them can also lead to weight regain or worsening blood sugar control.
“Millions of women are now using GLP-1 receptor agonists, but there remain important unanswered questions about their impact on fertility, pregnancy, and maternal and child health,” said Claire Meek, a professor at the Leicester Diabetes Research Centre and one of the study authors.
The expert panel behind the paper supported GLP-1 use before conception when needed to improve metabolic health in women with type 2 diabetes. But it recommended stopping the medication if pregnancy occurs.
Evidence was even more limited for women with type 1 diabetes or a history of gestational diabetes.
The key point is that this review does not show GLP-1 drugs can safely be continued throughout pregnancy. Instead, it offers some reassurance about a narrower situation: exposure shortly before or during early pregnancy, often before a woman realizes she is pregnant.
For women in that situation, the findings may be reassuring. But researchers say much more work is needed before the risks and benefits of GLP-1 use during pregnancy and breastfeeding are well understood.
Several authors reported financial relationships with pharmaceutical companies involved in the GLP-1 market, including Novo Nordisk and Eli Lilly.
The research was supported by public and nonprofit research programs, including the National Institute for Health and Care Research Leicester Biomedical Research Centre. One author was supported by a European Foundation for the Study of Diabetes-Novo Nordisk Foundation Future Leaders’ Award.