Reduced Gestational Diabetes Risk Observed with GLP-1 Use Before Pregnancy

A retrospective cohort study indicated that women using GLP-1 receptor agonist medications prior to pregnancy experienced a lower risk of gestational diabetes, although pre-eclampsia risk was elevated.

The incidence of gestational diabetes was observed to be 11% among women who had used a GLP-1 in the year leading up to pregnancy, compared to 53% among those who did not (P=0.005). Conversely, pre-eclampsia incidence was 68% versus 32%, respectively (P=0.023), according to findings presented by Dominick Lemas, PhD, of the University of Florida (UF) at the ObesityWeek annual meeting. The medications examined in the study were primarily liraglutide (Victoza, Saxenda), exenatide (Byetta), and dulaglutide (Trulicity), with one participant using semaglutide (Ozempic, Wegovy, Rybelsus).

The FDA advises that GLP-1 treatment should be stopped at least 2 months before conception to mitigate potential teratogenicity seen in animal studies, according to Lemas. However, adherence to these recommendations may vary, considering that almost half of pregnancies in the U.S. are unplanned. Health tracking apps like Shotlee can help monitor medication adherence and timing in relation to pregnancy planning.

Lemas noted that data is limited regarding how discontinuing a GLP-1 before conception affects fetal or maternal metabolic outcomes, especially concerning potential pre-pregnancy weight loss. Research indicates that in non-pregnant adults, discontinuing GLP-1 therapy can lead to rapid cardiometabolic rebound, affecting weight, blood pressure, and glycemic control within weeks.

This is particularly relevant in the context of pregnancy, as cardiometabolic rebound may coincide with early cardiovascular remodeling, thereby increasing the risk of adverse maternal-neonatal outcomes.

Study Details

Researchers analyzed data from over 28,000 women who delivered a singleton infant at the UF medical center between 2011 and 2021. The medical center serves a 13-county area in north central Florida, where nearly one-third (32.5%) of infants are born to mothers in rural counties. Furthermore, nine of these counties exhibited maternal death rates up to four times higher than the state average, along with elevated rates of preterm birth, infant mortality, and maternal smoking.

Out of 31 women who had taken a GLP-1 before pregnancy, 29 were matched with women not exposed to GLP-1s based on factors like previous diabetes diagnosis, obesity/overweight status, hypertension, maternal age at delivery, and race/ethnicity. The average age of participants was 31, and most had obesity, with an average BMI of 43 at admission.

Liraglutide was the most commonly used GLP-1, taken by half of the women in the 12 or 24 months before delivery. Approximately one-third had used exenatide, and the remainder had taken dulaglutide, with one woman using semaglutide in the 2 years before delivery. No participants had taken tirzepatide (Zepbound, Mounjaro), as it was not available during the study period.

Key Findings

• Gestational diabetes incidence was lower in those who had taken a GLP-1 in the 2 years before delivery (21%) compared to those not exposed (48%, P=0.027).
• However, 69% of women who had taken a GLP-1 in the 2 years before pregnancy experienced pre-eclampsia, versus 38% of those who had not (P=0.018).

C-section delivery rates were also significantly higher among those who had taken a GLP-1 in the 12 months (P=0.007) or 24 months (P=0.033) prior to delivery. Newborns' birthweight, gestational age, fetal growth, and likelihood of neonatal ICU admission were similar between the two groups.

Possible Mechanisms

Researchers suggest that improved insulin sensitivity and sustained weight loss before pregnancy may provide a lasting benefit, reducing gestational diabetes risk. Conversely, cardiometabolic rebound could contribute to increased blood pressure and gestational weight gain.

Sharon Herring, MD, MPH, of Temple University Lewis Katz School of Medicine, noted that COVID-19 infections have been linked to increased pre-eclampsia risk. Given that the study period included 2020-2021, it may be challenging to isolate the causes of higher pre-eclampsia rates without accounting for COVID-19 infection.

Herring emphasized the need for further investigation into pre-eclampsia cases, considering the small sample size and the patients' demographics and risks, which may limit the generalizability of the study. The study also lacked data on glycemic control trajectories, blood pressure patterns, lifestyle factors, pre-pregnancy weight loss, and medication adherence, dosage, or duration.

Additionally, Herring noted that the absence of data on semaglutide or tirzepatide limits generalizability, particularly for women taking a GLP-1 for obesity, as exenatide and dulaglutide are primarily indicated for diabetes control.