Comment on: “Gestational Weight Gain and Pregnancy Outcomes After GLP-1 Receptor Agonist Discontinuation”

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are commonly used to treat obesity and type 2 diabetes by improving glycemic control and promoting weight loss. Rates of prepregnancy obesity and diabetes are rising, and both are associated with pregnancy complications and long-term metabolic disease in children. GLP-1RAs are increasingly used by women of reproductive age, but are not recommended during pregnancy because animal studies have reported fetal structural abnormalities, growth restriction, and pregnancy loss. Discontinuation of GLP-1RA therapy can lead to weight regain and worsening glycemic control, raising the possibility that stopping treatment before or early in pregnancy could contribute to excess gestational weight gain and related complications. This study evaluated gestational weight gain and related outcomes among individuals exposed to GLP-1RAs in the prepregnancy or early pregnancy period compared with similar unexposed individuals. This retrospective cohort study included singleton pregnancies delivered between June 2016 and March 2025 within the Mass General Brigham health system. Pregnancies were categorized as exposed if at least one GLP-1RA medication order was documented between 3 years before conception and 90 days after conception; all others were classified as unexposed. Pregnancies with multiple gestations, prior bariatric surgery, missing gestational age, or implausible anthropometric data were excluded. The primary outcome was gestational weight gain. Secondary outcomes included excess gestational weight gain, neonatal birth weight outcomes, and obstetric outcomes, including preterm delivery, cesarean delivery, gestational diabetes, and hypertensive disorders of pregnancy. Propensity score matching was used to compare exposed and unexposed pregnancies with similar clinical and demographic characteristics. Of the 149,790 pregnancies delivered during the study period, 655 were exposed to a GLP-1RA within the window of interest. After exclusions and propensity score matching, 448 exposed pregnancies were matched to 1344 unexposed pregnancies in the gestational weight gain cohort. In this cohort, mean gestational weight gain was higher among individuals with prior GLP-1RA exposure compared with unexposed individuals (13.7 vs. 10.5 kg; difference, 3.3 kg; 95% CI: 2.3-4.2). The risk of excess gestational weight gain was also higher in the exposed group (65% vs. 49%; RR, 1.32; 95% CI: 1.19-1.47). Risks of large- or small-for-gestational-age birth weight were similar between groups, although the mean birth weight percentile was modestly higher among exposed pregnancies. GLP-1RA exposure was associated with higher risks of preterm delivery (RR, 1.34), gestational diabetes (RR, 1.30), and hypertensive disorders of pregnancy (RR, 1.29), but not cesarean delivery. Results were similar across secondary and sensitivity analyses. GLP-1RA exposure before pregnancy, followed by discontinuation in early pregnancy, was associated with greater gestational weight gain and higher risks of preterm delivery, gestational diabetes, and hypertensive disorders of pregnancy. No increased risk of large- or small-for-gestational-age birth weight or cesarean delivery was observed. Strengths include the large health system cohort and detailed clinical data used to define exposures and outcomes. Limitations include the retrospective design, potential residual confounding, and reliance on medication orders that may not reflect actual medication use. (Summarized from 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)