Women with obesity who stopped taking GLP-1 receptor agonists (RAs) early in or before pregnancy gained seven more pounds than those who were never prescribed the weight-loss medications, according to a new observational study published in JAMA. These women also had a greater risk for adverse outcomes such as gestational diabetes, hypertensive disorders of pregnancy, and preterm delivery.

The American College of Obstetricians and Gynecologists recommends weight management and glucose control prior to pregnancy for women with diabetes or obesity, as the conditions can raise the risk for maternal and fetal complications.

But the effect of stopping GLP-1 RAs before gestation has been unclear, said Jacqueline Maya, MD, a pediatric endocrinologist at Mass General Brigham and instructor of pediatrics at Harvard Medical School in Boston.

Given the documented weight gain associated with discontinuing GLP1 RAs outside of pregnancy, the increases shown in the study were not unexpected, Maya told Medscape Medical News.

“We were reassured that there were no changes in infant birth weight; however, we were concerned that there were increases in the risk of obstetric outcomes,” she said.

However, given the limitations of observational research, Maya and her colleagues could not determine that discontinuing the medications caused the adverse outcomes.

“We do not believe the adverse outcomes were due to the medications themselves,” she said. “A plausible explanation for our findings is that the adverse obstetric outcomes are secondary to the greater weight gain, which occurred after stopping the medications.”

Maya and colleagues reviewed data from 1792 singleton pregnancies (mean age, 34 years; 50% White individuals; 30% Hispanic individuals) between June 2016 and March 2025 at a single academic health system. Of these, 448 were exposed to GLP-1 RAs in the 3 years prior to conception and discontinued them before or during pregnancy. The remaining women who were unexposed served as matched control individuals. Overall, 84% of women had obesity and 23% had preexisting diabetes.

The mean BMI for both groups was a little over 36, although group differences varied between classes of weight. Fewer GLP-1 RA users had a healthy BMI and more had overweight or obesity, while severe obesity was more common in the control group. Both groups had similar rates of chronic hypertension, but preexisting diabetes was more common among women taking GLP-1 RAs.

Maya and colleagues also tracked hypertensive disorders of pregnancy, gestational diabetes, excess weight gain, preterm delivery, cesarean delivery, and other birth outcomes like birth weight percentile and small for gestational age.

Women who had been on the drugs gained an average of seven more pounds during pregnancy than the control group (an average of approximately 30 lb vs 23 lb; P < .001). They were also more likely to have excess gestational weight gain (risk ratio [RR], 1.32; 95% CI, 1.18-1.47).

Women who used GLP-1 RAs also were more likely to develop hypertensive disorders of pregnancy (RR, 1.26; 95% CI, 1.12-1.49), gestational diabetes (RR, 1.30; 95% CI, 1.01-1.68). Regarding fetal outcomes, the risk for preterm delivery was higher (RR, 1.34; 95% CI, 1.06-1.69), and infants had a higher mean birth weight percentile.

No significant differences were noted between the groups in cesarean delivery, birth length, or large or small for gestational age.

The current study findings suggest that clinicians should monitor more closely patients who are discontinuing the weight loss drugs when they become pregnant for complications and weight gain, Maya said. More research is needed to determine the best strategies to mitigate these risks, she said.

Maya said many more questions need to be answered, including the best timing for discontinuation of GLP-1 RAs to ensure optimal outcomes.

“We will need to exclude any potential long-term impact on childhood metabolic health,” she said. “We know these medications are beneficial for weight, blood sugar, and cardiovascular health, so I think we need to focus on finding ways to support women who come off these medications for pregnancy.”

Clinical Implications

Amy M. Valent, DO, medical co-director of the diabetes and pregnancy program at Oregon Health and Science University in Portland, Oregon, who was not involved in the current study, said she was surprised by the lack of birthweight differences given the higher rates of gestational weight gain and gestational diabetes in the GLP-1 RA cohort, as both are independently associated with large for gestational age infants.

In clinical practice, the results suggest that discontinuation of GLP-1 RAs can affect pregnancy if lifestyle and nutritional interventions are not established prior to discontinuation, Valent said.

“It is important to discuss risks and benefits of different options for optimizing health prior to pregnancy to reduce perinatal outcomes, including medication, nutrition, lifestyle, and sleep habits,” she said. “Starting a GLP-1 RA doesn’t provide an excuse to avoid healthy lifestyle behaviors.”

Maya said she and her colleagues plan to conduct future research on the risks and benefits associated with starting GLP-1 RAs before pregnancy.

The study and Maya were supported by American Diabetes Association (ADA) Women’s Health and Diabetes Research Junior Faculty Development Award and the Massachusetts General Hospital Physician-Scientist Development Award. Maya also reported receiving an ADA honorarium for presenting the findings at the ADA Scientific Sessions in 2025.

Valent disclosed no financial conflicts of interest.