GLP-1 Discontinuation during Pregnancy tied to excessive gestational weight gain, preterm birth: JAMA
Researchers have found in a new study that discontinuation of GLP-1 receptor agonists before or early in pregnancy was linked to greater gestational weight gain and higher risks of preterm birth, gestational diabetes, and hypertensive disorders. Since GLP-1 drugs are contraindicated in pregnancy, their recommended discontinuation was associated with increased pregnancy-related complications in women, primarily those with obesity. The study was published in JAMA by Jacqueline M. and colleagues.
This analysis illustrated that GLP-1RA exposure was associated with increased gestational weight gain and heightened risks of preterm delivery, gestational diabetes, and hypertensive disorders, highlighting potential unintended consequences of discontinuing these agents proximal to conception. This cohort study aims to compare gestational weight gain in pregnancies that are exposed to GLP-1RAs before or during early pregnancy with those unexposed. Secondary objectives include excess gestational weight gain, birth weight parameters, preterm delivery, cesarean delivery, gestational diabetes, and hypertensive disorders of pregnancy.
This retrospective cohort study analyzed 149,790 singleton pregnancies delivered between June 1, 2016, and March 31, 2025, within a single academic health system. A total of 1,792 pregnancies were included in the matched analysis, comprising 448 GLP-1RA–exposed and 1,344 unexposed pregnancies matched using propensity score methods in a 1:3 ratio. Exposure was defined as a GLP-1RA prescription recorded between 3 years before conception and 90 days after conception. The mean maternal age in the exposed group was 34.0 ± 4.7 years, with a mean prepregnancy BMI of 36.1 ± 6.5. Obesity was present in 84%, and pre-existing diabetes was present in 23% of exposed pregnancies, reflecting a high-risk population.
Key findings
GLP-1RA–exposed pregnancies had substantially higher gestational weight gain, with a mean of 13.7 ± 9.2 kg compared with 10.5 ± 8.0 kg for unexposed pregnancies, for a difference of 3.3 kg (95% CI, 2.3–4.2; P < .001).
Excess gestational weight gain affected 65% of exposed pregnancies versus 49% of unexposed pregnancies, for a corresponding risk ratio of 1.32 (95% CI, 1.19–1.47).
The exposed group also had a higher mean birth weight percentile (58.4% vs 54.8%; difference 3.6%; 95% CI, 0.2–6.9).
Risks were increased for preterm delivery (17% vs 13%; RR 1.34; 95% CI, 1.06–1.69), gestational diabetes (20% vs 15%; RR 1.30; 95% CI, 1.01–1.68), and hypertensive disorders of pregnancy (46% vs 36%; RR 1.29; 95% CI, 1.12–1.49).
There were no significant differences in birth length, large or small for gestational age classification, or cesarean delivery rates.
In this analysis, exposure to GLP-1 receptor agonist and its discontinuation around conception were associated with higher gestational weight gain and increased risks of preterm delivery, gestational diabetes, and hypertensive disorders of pregnancy. These results emphasized the importance of active reproductive planning and individualized clinical strategies in women on GLP-1RAs aimed at decreasing adverse maternal and neonatal outcomes.
Reference:
Maya J, Pant D, Fu Y, et al. Gestational Weight Gain and Pregnancy Outcomes After GLP-1 Receptor Agonist Discontinuation. JAMA. Published online November 24, 2025. doi:10.1001/jama.2025.20951
