Discontinuing GLP-1 receptor agonists before or early in pregnancy was associated with greater gestational weight gain and higher risks of diabetes, hypertension, and preterm birth.
A study published in JAMA examined the association between discontinuing GLP-1 receptor agonists (GLP-1RAs) before or early in pregnancy and subsequent gestational weight gain and pregnancy outcomes. The retrospective cohort analysis included 1,792 matched pregnancies within the Mass General Brigham system from 2016 to 2025. The analysis prioritized individuals with obesity, reflecting the clinical population most likely to be prescribed GLP-1 therapy for weight or glycemic control.1,2
According to the press release, clinical uncertainty persists regarding how stopping these medications affects pregnancy outcomes. Jacqueline Maya, MD, the study’s lead author, stated, “We sought to assess how such discontinuation affects weight gain and outcomes during pregnancy.”
The investigators identified individuals who had a GLP-1RA prescription within three years before conception or up to 90 days after conception, then matched them to three unexposed pregnancies with similar demographic and clinical characteristics. Mean gestational weight gain differed significantly between groups. Individuals who discontinued GLP-1 therapy gained 13.7 kg on average, compared with 10.5 kg in the unexposed cohort, representing a mean difference of 3.3 kg.
Excess gestational weight gain, defined according to Institute of Medicine recommendations, occurred in 65% of exposed pregnancies versus 49% of unexposed controls.
This pattern was consistent across secondary and sensitivity analyses, including subanalyses of semaglutide and liraglutide.
Discontinuation of GLP-1 therapy was also associated with increases in adverse pregnancy outcomes. In the obstetric cohort, the risk of gestational diabetes was 20% in the exposed group and 15% in the unexposed group (RR, 1.30). The risk of hypertensive disorders of pregnancy reached 46% in exposed individuals compared with 36% in unexposed matches (RR, 1.29). Additionally, preterm delivery occurred in 17% of exposed pregnancies compared with 13% of unexposed controls (RR, 1.34).
The study found no significant differences in cesarean delivery, large-for-gestational-age birth weight, small-for-gestational-age birth weight, or birth length between groups. Although birth weight percentile was modestly higher among GLP-1–exposed pregnancies, this shift did not translate into clinically notable differences in newborn size.
The findings support prior evidence demonstrating weight regain and changes in metabolic parameters after discontinuation of GLP-1 therapy. The study team noted that these physiologic changes could contribute to heightened pregnancy risks.
Senior author Camille E. Powe, MD, commented on the importance of balancing the risks and benefits of GLP-1 use in individuals who may plan pregnancy. “Additional studies are needed on the balance of pre-pregnancy benefits of GLP-1s with the risks associated with interrupting them for pregnancy,” she said. “We need to do more research to find ways to help manage weight gain and reduce risks during pregnancy when stopping GLP-1 medications.”
Given rapidly increasing GLP-1RA use among reproductive-aged individuals, obstetric and endocrine clinicians may need to incorporate counseling that anticipates weight regain and metabolic changes after discontinuation. The study suggests that individuals who stop GLP-1 therapy near or shortly before conception may require increased monitoring for gestational diabetes and hypertensive disorders and more intensive support related to gestational weight gain.
The authors noted that additional research is needed to determine whether preconception weight loss induced by GLP-1 therapy offers a net benefit despite the need to discontinue treatment during pregnancy. Long-term effects on maternal weight retention and offspring metabolic health remain unknown.
Overall, the study provides new data to inform risk assessment and individualized care planning for patients entering pregnancy after recent GLP-1RA use.
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