Discontinuing GLP-1RAs during pregnancy tied to Weight Gain and Adverse Pregnancy Outcomes: JAMA Study

GLP-1RA is an established class of incretin-based therapies used primarily in type 2 diabetes that improves glycemic control by enhancing glucose-dependent insulin secretion. As GLP-1RAs are currently contraindicated during pregnancy, many individuals cease treatment immediately upon planning or discovering a pregnancy. However, there is a significant clinical gap regarding how this sudden discontinuation affects metabolic health and weight trajectories during gestation. The study, led by Kaitlyn Jame of the Department of Obstetrics and Gynecology at Massachusetts General Hospital, Boston, and colleagues, aimed to compare gestational weight gain and various pregnancy outcomes between individuals exposed to GLP-1RAs before or during early pregnancy and those with no such exposure.

The retrospective cohort study analyzed 149,790 single-fetus pregnancies delivered within a single academic health system between June 2016 and March 2025. Researchers matched 448 pregnancies exposed to GLP-1RA orders between three years before and 90 days after conception to 1,344 unexposed pregnancies using propensity score matching. The population predominantly consisted of women with obesity (84%), with a mean prepregnancy BMI of 36.1. Analytical methods focused on the primary outcome of gestational weight gain, alongside secondary measures such as birth weight percentiles and hypertensive disorders.

Key Findings

• Exposed individuals experienced a mean gestational weight gain of 13.7 kg, compared to 10.5 kg in the unexposed group—a statistically significant difference of 3.3 kg.
• GLP-1RA withdrawal in exposed women significantly elevates risks of preterm delivery (17% vs 13%; RR, 1.34) and gestational diabetes (20% vs 15%; RR, 1.30)
• The risk of excess gestational weight gain was 32% higher in the GLP-1RA-exposed women (65% vs 49%; RR, 1.32).
• Hypertensive disorders of pregnancy were notably more frequent in the exposed group (46% vs 36%; RR, 1.29).
• While mean birth weight percentiles were higher in the exposed group (58.4% vs 54.8%), there were no significant differences in birth length or cesarean delivery rates.

GLP-1RAs are currently contraindicated during pregnancy; their abrupt discontinuation represents a significant public health concern. These findings are profound for obstetricians and endocrinologists managing patients on GLP-1 therapy. The data suggest that the physiological changes following medication cessation may predispose patients to metabolic instability during pregnancy. Clinicians should consider closer monitoring and targeted nutritional support for patients who have recently discontinued these agents to mitigate the risks of excess weight gain and associated hypertensive disorders.

As the author says, these associations highlight a critical need for "guiding obstetric care and treatment decisions for women with prior GLP-1 receptor agonist use."

Reference

Maya J, Pant D, Fu Y, et al. Gestational Weight Gain and Pregnancy Outcomes After GLP-1 Receptor Agonist Discontinuation. JAMA. 2025;334(24):2186–2196. doi:10.1001/jama.2025.20951