Study Looks at GLP-1 Use in Pregnancy and Gestational Weight Gain

WASHINGTON — GLP-1 receptor agonist use for weight loss early in pregnancy was associated with a lower likelihood that gestational weight gain would be below recommended levels, according to a retrospective cohort study.

For women taking GLP-1 drugs for weight management, there was a significant decrease in the odds of gestational weight gain below recommended Institute of Medicine (IOM) levels during early pregnancy (adjusted OR 0.29, 95% CI 0.12-0.70), reported Nishita Pondugula, MD, MS, a first-year resident at Duke University Medical Center in Durham, North Carolina, at the American College of Obstetricians and Gynecologists annual meeting.

Prepregnancy-only exposure did not have a significant effect on gestational weight gain, which Pondugula said may indicate “slowing of rebound weight gain after more time has passed since GLP-1 cessation.” She also noted that there were no significant differences when looking at exceeding IOM recommendations. Weight re-gain is common after stopping GLP-1 agents.

In addition, exposure to GLP-1 drugs up to 1 year prior to pregnancy did not significantly affect the odds of developing hypertensive disorders of pregnancy for women taking the drugs for pregestational diabetes (aOR 0.72, 95% CI 0.42-1.25) or weight management (aOR 0.83, 95% CI 0.45-1.52).

Pondugula pointed to a signal for risk of fetal death after GLP-1 exposure in the weight-management cohort (2.9% vs 0.5%), though this did not reach statistical significance, and that signal was not present in the diabetes cohort. Some animal studies have raised concerns about fetal death and GLP-1 medications, though observational research in humans has not shown an increased risk.

There’s extremely limited evidence on the effects of GLP-1 drugs in pre-pregnancy and early pregnancy, but an increasing number of patients are using the drugs for both diabetes and weight management.

A previous analysis of health records that primarily included women with obesity suggested that the recommended discontinuation of GLP-1 receptor agonists during pregnancy was associated with more gestational weight gain and higher risks of pregnancy complications. In a small retrospective study, using GLP-1 agents before pregnancy was linked to a lower risk of gestational diabetes, but not preeclampsia.

Nikki Zite, MD, MPH, an ob/gyn at the University of Tennessee Graduate School of Medicine in Knoxville, who was not involved with the research, said that with “the increase in use of these medications across the board, but especially in reproductive-age women, it is important that we continue to evaluate the potential risks and benefits to provide evidence-based guidance.”

She told MedPage Today that she was not surprised that fewer patients gained below the recommended amount of weight, considering the weight gain seen when patients discontinue GLP-1 agents and typical weight gain seen during pregnancy.

While the researchers didn’t find a significant association between the medications and hypertensive disorders of pregnancy, Zite said that “given the biologic plausibility and the non-significant risk reduction they noted, further investigation is warranted.”

This study sought to evaluate the effects of exposure to GLP-1 receptor agonists up to 1 year prior to pregnancy on maternal gestational weight gain and development of hypertensive disorders of pregnancy for women taking the drugs for weight management or diabetes.

Pondugula and team queried electronic medical records for all deliveries within the Yale New Haven Health system between 2014 and 2024 with hand abstraction to confirm GLP-1 drug exposure and dates of use up until 1 year prior to pregnancy. In all, 243 people were exposed to GLP-1 medications.

The researchers included 103 patients who had used GLP-1 drugs for diabetes and 175 patients in a control group, and 140 patients who used the drugs for weight management and 200 patients in a control group.

Semaglutide (Ozempic, Wegovy) was the most commonly used GLP-1 medication (63%). The last use of a GLP-1 medication was a mean 14 days prior to pregnancy. For those who used the drugs in the prepregnancy period, discontinuation was a mean 142 days prior to pregnancy. For those who had exposure in early pregnancy, the last use was a mean 53 days into pregnancy.

The primary outcome was maternal gestational weight gain, transformed based on weekly IOM recommendations and accounting for gestational age at delivery. The co-primary outcome was diagnosis of a hypertensive disorder of pregnancy, including gestational hypertension, preeclampsia with or without severe features, superimposed preeclampsia, eclampsia, and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome.

Among the cohort with pregestational diabetes, Black patients were significantly more likely to be exposed to GLP-1 medications, as were those with a prepregnancy body mass index (BMI) of ≥30, and the control group was significantly more likely to be using metformin. In the weight-management cohort, those with GLP-1 drug exposure were significantly more likely to have chronic hypertension or polycystic ovary syndrome and significantly less likely to have a prepregnancy BMI of ≥30.

Future research should clarify the optimal timing of peripregnancy GLP-1 receptor agonist cessation and the safety of continuation into pregnancy, especially for those taking the drugs for pregestational diabetes, Pondugula said.