Women taking semaglutide (a GLP-1 receptor agonist medication) before and during pregnancy face significantly higher risks for gestational diabetes, excessive weight gain, and cesarean delivery compared to those who never used the drug, according to a new national database study. The findings raise important questions about medication planning for women of reproductive age who are managing weight or diabetes.

What Does the Research Show About GLP-1 Use in Pregnancy?

Researchers at the University of Rochester analyzed electronic medical records and pharmacy data from women aged 18 to 45 years with overweight or obesity who delivered between January 2022 and January 2026. They compared three groups: those who used semaglutide before and into pregnancy, those who stopped before conception, and those who never used it.

The results were striking. Among the 429 women who continued semaglutide exposure during pregnancy, compared with 2,203 nonusers, pregnancy-exposed users experienced an average of 5.12 kilograms (roughly 11 pounds) greater gestational weight gain. They also faced significantly elevated risks for gestational diabetes, excessive fetal growth, and cesarean delivery. Even women who stopped semaglutide before pregnancy (801 participants) showed similar elevated risks for these complications.

The medication carries a current FDA warning advising women to discontinue semaglutide at least two months before attempting to conceive. This warning is based on animal research linking the drug to miscarriage, impaired fetal growth, and birth defects. However, unintended pregnancy exposure is likely common, given that approximately 40% of U.S. pregnancies are unplanned and strict contraceptive use is not mandated during GLP-1 treatment.

Why Does Weight Rebound After Stopping the Drug Matter?

The research suggests a surprising mechanism: the pregnancy complications may not stem from the drug itself reaching the baby, but rather from what happens after women stop taking it. When semaglutide is discontinued, women often experience rapid weight regain and a return of metabolic disturbances. This weight rebound appears to be a key driver of adverse pregnancy outcomes.

"One important mechanism may be weight rebound after semaglutide discontinuation. Excessive gestational weight gain is a well-established risk factor for a range of adverse pregnancy outcomes, and women who stop semaglutide often experience rapid weight regain," said Yang Yu, PhD, MPH, MNS, an assistant professor at the University of Rochester School of Nursing.

Yang Yu, PhD, MPH, MNS, Assistant Professor at University of Rochester School of Nursing

This finding aligns with commentary from reproductive medicine specialists. Henriette Svarre Nielsen, MD, DMSc, chair and professor of obstetrics and gynecology at the University of Copenhagen, noted that recent real-world studies from both the United States and Denmark point to the same conclusion: the risks are not from the drug reaching the fetus, but from the metabolic changes that occur after discontinuation.

What Should Women Know About GLP-1 Use and Fertility?

The situation is complicated by the fact that GLP-1 medications may actually enhance fertility. Animal studies suggest the drugs can improve ovulation by reducing ovarian inflammation and oxidative stress. Additionally, weight loss from GLP-1 use can improve metabolic health and menstrual regularity, potentially making conception easier. This paradox means women may become pregnant more readily while on these medications, even without strict contraceptive use.

Another practical concern: gastrointestinal side effects such as vomiting, which are common with GLP-1 drugs, may reduce the effectiveness of oral contraceptives. This adds another layer of unintended pregnancy risk for women using these medications.

Steps to Take if You're Using GLP-1 Medications and Planning Pregnancy

• Follow the Two-Month Rule: Discontinue semaglutide at least two months before attempting to conceive, based on the drug's long half-life and the time required for it to clear from your body. This recommendation is the current standard, though researchers note more evidence is needed to determine the optimal timing.
• Use Effective Contraception: Because GLP-1 medications may enhance fertility through weight loss and metabolic improvements, and because gastrointestinal side effects can reduce oral contraceptive effectiveness, discuss reliable contraceptive options with your healthcare provider during GLP-1 treatment.
• Consult Your Healthcare Team: If you're taking semaglutide for diabetes management, work closely with your doctor to weigh the potential risks and benefits before conception. The decision should be individualized based on your specific health situation.
• Seek Reassurance if Unplanned Pregnancy Occurs: If you become pregnant unexpectedly while on GLP-1 medication, experts emphasize that women need reassurance rather than alarm. Discuss your specific situation with your healthcare provider rather than assuming the worst.

Researchers emphasize that more investigation is needed. "We need to better understand the biological mechanisms linking semaglutide use and discontinuation to pregnancy outcomes, determine whether there are effects on long-term child health, clarify the risk of congenital malformations in larger human studies, and identify the optimal timing for discontinuation before pregnancy," Yu noted.

The bottom line: while GLP-1 medications like semaglutide are increasingly popular for weight management and diabetes control, women of reproductive age should have a clear conversation with their healthcare provider about pregnancy planning. The risks appear to be tied to weight rebound and metabolic changes after stopping the medication rather than direct fetal exposure, but the evidence is still evolving. With proper planning, communication, and contraceptive use, women can make informed decisions about their reproductive health while managing their weight and metabolic conditions.