Discontinuing GLP-1s Before or Early in Pregnancy Tied to Weight Gain, Pregnancy Complications

Discontinuation of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) before conception or during early pregnancy was associated with greater gestational weight gain and increased risks of preterm delivery, gestational diabetes, and hypertensive disorders of pregnancy in a cohort comprised primarily of women with obesity^, according to findings published today in JAMA.¹

Balancing Benefits, Risks of GLP-1 RAs

Optimizing hyperglycemia and weight before pregnancy is strongly recommended, as diabetes and obesity elevate the risk of pregnancy complications and long-term metabolic disease in offspring. Most commonly used to treat obesity and type 2 diabetes, GLP-1 RAs help to improve glycemic control, promote weight loss, and offer cardiovascular benefits.² Their use has grown among women of reproductive age for reducing both weight and glucose levels.¹

However, these therapies are not recommended during pregnancy due to animal toxicity studies showing fetal structural abnormalities, intrauterine growth restriction, and embryofetal mortality. As a result, most patients discontinue GLP-1 RAs before conception or upon learning of a pregnancy. Despite their increasing use, data on associations between GLP-1 RA exposure and adverse pregnancy outcomes beyond birth defects remain limited.

Discontinuation of GLP-1 RAs outside of pregnancy is known to cause weight regain and worsening hyperglycemia. If stopping therapy before or early in pregnancy contributes to excess gestational weight gain, this could negatively impact maternal and offspring health, as excess gestational weight gain is linked to adverse maternal and neonatal outcomes.

Assessing GLP-1 RA Exposure and Pregnancy Outcomes

To evaluate these concerns, the researchers conducted a study assessing gestational weight gain and related secondary outcomes among individuals exposed to GLP-1 RAs in the prepregnancy and early pregnancy period compared with unexposed individuals with similar baseline characteristics. This retrospective cohort study included singleton pregnancies delivered between June 1, 2016, and March 31, 2025, at Mass General Brigham, using data from the health system’s Enterprise Data Warehouse and Research Patient Data Registry.

The primary exposure was defined as at least 1 GLP-1 RA prescription documented in the electronic health record between 3 years before and 90 days after conception. Individuals without any GLP-1 RA prescriptions during this period were considered unexposed. The researchers used propensity score matching to match each exposed pregnancy with 3 unexposed pregnancies. Only one pregnancy per patient was included, with exposed pregnancies prioritized.

The primary outcome was gestational weight gain, calculated as the difference between the last recorded weight within 1 week of delivery and prepregnancy weight. Secondary outcomes included excess gestational weight gain, neonatal birth weight outcomes, and obstetric complications. Three analytic cohorts were constructed: gestational weight gain, birth weight, and obstetric outcomes.

Increased Gestational Weight Gain, Pregnancy Complications Associated With GLP-1 RAs

Among 149,790 eligible pregnancies, 655 involved GLP-1 RA exposure. After exclusions and matching, 448 exposed pregnancies were matched with 1344 unexposed pregnancies in the gestational weight gain cohort; 442 exposed were matched with 1326 unexposed in the birth weight cohort; and 566 exposed were matched with 1698 unexposed pregnancies in the obstetric cohort.

Exposed pregnancies had greater gestational weight gain (mean, 13.7 [SD, 9.2] kg) than the matched unexposed pregnancies (mean, 10.5 [SD, 8.0] kg), with a difference of 3.3 kg (95% CI, 2.3-4.2; P < .001). They also had higher rates of excess gestational weight gain (65% vs 49%; risk ratio [RR], 1.32; 95% CI, 1.19-1.47) and higher mean birth weight percentile (58.4% vs 54.8%; difference, 3.6%; 95% CI, 0.2%-6.9%).

Exposed pregnancies were also at increased risk 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). However, no significant differences were observed for birth length, large or small for gestational age outcomes, or cesarean delivery rates.

Unanswered Questions and Future Research Priorities

The researchers acknowledged several limitations, including the potential for residual confounding inherent to all observational studies. Additionally, the findings may have limited generalizability because the Mass General Brigham population is older, less likely to have a BMI of 25 or higher, less representative of Black and Latino individuals, and less likely to have public insurance. Still, they emphasized that the findings highlight important clinical considerations for patients using GLP-1 RAs before pregnancy.

“…more data are needed on the implications of GLP-1 RA discontinuation-associated gestational weight gain for long-term weight retention in mothers and programming effects in offspring that may be independent of birth weight,” the authors wrote. “…future studies should define clinical approaches to mitigate excess gestational weight gain in individuals with obesity and diabetes who were using GLP-1 RAs before pregnancy.”

References

1. 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
2. FDA. Byetta (Exenatide) highlights of prescribing information. Last revised May 2025. Accessed November 24, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/021773s050lbl.pdf