Weight-loss medications are associated with an increased risk of preterm birth in women with pre-existing diabetes

Weight-loss medications have been associated with an increased risk of preterm birth among women who took them before pregnancy or during early pregnancy to treat preexisting diabetes.

However, a large study of more than 750,000 pregnancies found that weight loss medication use was not associated with preterm birth or other birth complications.

study authors, in today’s (Wednesday) publication Open human reproduction, One of the world’s leading reproductive medicine journals, their findings show that it is diabetes rather than medication that may increase the risk of premature birth.

Weight-loss drugs such as semaglutide (brand names: Ozempic, Vigovi) and liraglutide (Saxenda) belong to a class of drugs called GLP-1 receptor agonists (GLP-1 RAs), originally developed to treat type 2 diabetes. They work mainly by suppressing appetite and have been proven to be useful in helping people lose weight quickly. However, there is no evidence to suggest that taking them during pregnancy is safe.

“GLP-1 RA therapy has rapidly become a prescription drug worldwide in the past few years, but current guidelines should recommend weekly planning to prevent pregnancy. In early-stage model organism studies, and there is no real-world evidence, however, due to its widespread use, Spontaneous exposure in early pregnancy is inevitable, and there is no evidence to guide clinical advice when it occurs.”

The researchers decided to investigate the relationship between women exposed to GLP-1 RA therapy during the conception period and the risk of complications such as preterm birth (birth before 37 weeks), preeclampsia, gestational diabetes, large-for-gestational-age delivery, stillbirth, and placental problems.

They analyzed data from the Danish health registers for 756,636 singleton pregnancies nationwide among 480,231 women resulting in births between 1 October 2009 and 31 December 2023. Accidental exposure to medication. This 16-week window captures the period when the mother may not know she is pregnant and the early stages of organ development in the fetus. A total of 529 pregnancies were exposed to GLP-1 RAs during conception.

The researchers adjusted their results for maternal age, body mass index (BMI), smoking status, geographic region, education, diabetes, and month and year of pregnancy to control for seasonal or other trends.

The paper’s first author, Dr. Catherine Hayward, a PhD student in the same department, said: “We made some very important findings that have implications for future studies, such as randomized controlled trials of GLP-1 RA use in pregnancy, and for clinical advice.

“We found that the drug was associated with an increased risk of preterm birth, but the risk was only present when the drug was used to treat diabetes, not for weight management. This suggests that the underlying diabetes condition, rather than the drug, may be driving this association.”

The researchers found that women who took GLP-1 RAs had higher rates of multiple birth defects, but after adjusting for factors that could have affected the results, they found a greater risk of preterm birth only in women who took either liraglutide or semaglutide to treat diabetes. Compared with women not taking GLP-1 RAs, the increased risk was 70% for liraglutide and 84% higher for semaglutide. This means that among women who had previously taken semaglutide, the drug was associated with an approximately 11% higher risk of preterm birth. Liraglutide showed an increased risk of 9%.

Future studies should consider the reason a woman is prescribed this drug, as the risks differ between women using GLP-1 RAs for diabetes compared to weight management. This is one of the first studies to examine GLP-1 RA exposure in early pregnancy with a prescription rationale. As more evidence accumulates, these findings will guide clinical advice for women who have been inadvertently exposed to GLP-1 RAs in early pregnancy. In Denmark, about 70% of people who use weight loss pills are women and so it is inevitable that some take them without knowing they are pregnant.

Professor Henriette Sverre Nielsen, Department of Obstetrics and Gynecology, Copenhagen University Hospital Hvidovre

However, she said more studies were needed and it was too soon to change the recommendation to stop GLP-1 RAs before pregnancy, or implement advice, unless women take them.

The strength of the study is its large size. Limitations include the fact that the results cannot show that GLP-1 RAs cause preterm birth, only that they are associated with it. In addition, there is no data showing that women actually took the medication after they received their prescriptions back. However, women in Denmark need to pay for injecting GLP-1 RAs, even though there is a government subsidy for diabetes treatment. For example, a 1mg injection of Vigovi or Ozempic (semglutide) costs around €180 and €114 respectively, including the subsidy for diabetes treatment.

“Because of the high cost, we assume that compliance in women prescribed GLP-1 RAs is very high,” said Dr. Hviid.

In an invited commentary accompanying the article, Dr. Ye Zhou and Monique Hederson, from Kaiser Permanente Northern California and the Upstream Prevention and Diabetes Mellitus Center, in Pleasanton, California, USA, wrote that the study findings “complement and extend the evidence for the safety of GRALP-1 replacement.”

They continue: “For clinicians, the Hviid et al (2026) study may inform preconception and preconception counseling. The observation that the increased prenatal risk was limited to women on diabetes treatment, not to those using GLP-1 receptor agonists for weight management, supports a more balanced, individualized discussion with patients who may have experience with the exception. In diabetic patients, the study preconceived and during pregnancy It reinforces the importance of recognizing diabetes as an important risk factor for birth complications to prioritize metabolic health and glycemic management.”