Peripregnancy GLP-1 Exposure Not Linked to Hypertensive Disorders of Pregnancy in New Cohort Study

Peripregnancy exposure to glucagon-like peptide-1 receptor agonists (GLP-1 RAs) was not associated with hypertensive disorders of pregnancy among patients using the medications for either pregestational diabetes or weight management, according to findings presenting during a late-breaking abstract session at the 2026 ACOG Annual Clinical & Scientific Meeting (ACSM) being held May 1-3 and simultaneously published in Obstetrics & Gynecology.

The study also found that among patients using GLP-1 RAs for weight management, exposure up to 1 year before pregnancy or during early pregnancy was associated with lower odds of gestational weight gain below Institute of Medicine recommendations. Investigators suggested this may reflect rebound weight gain after medication discontinuation.

The findings may be relevant for primary care clinicians who prescribe or monitor GLP-1 RAs in reproductive-aged patients, particularly as use of this medication class has increased for type 2 diabetes and obesity. The authors noted that weight loss may increase spontaneous pregnancy rates, increasing the likelihood of exposure during the peripregnancy period.

“Additional studies are needed to guide GLP-1RA use in pregnancy and to better elucidate any risks of exposure,” investigators wrote.

Study design and population

Nishita Pondugula, MD, MS, and colleagues conducted a retrospective cohort study of patients who delivered between 2014 and 2024 at a large medical center with 4 delivery hospitals and had documented GLP-1 RA exposure up to 1 year before pregnancy. Exposure stop dates were confirmed through manual medical record abstraction.

Patients were classified according to indication for use: pregestational diabetes or weight management. The exposed cohort included 243 patients, of whom 103 used a GLP-1 RA for pregestational diabetes and 140 used one for weight management. Overall, 159 patients, or 65.4%, had evidence of exposure during pregnancy, while 84 had prepregnancy-only exposure.

Unexposed comparator groups included 175 patients with pregestational diabetes treated with medications other than GLP-1 RA and 200 patients in the weight-management control group. The weight-management control group included 100 patients with body mass index 30 to 39.9 and 100 patients with body mass index 40 or higher.

The 2 primary outcomes were gestational weight gain and hypertensive disorders of pregnancy. Gestational weight gain was categorized as below, meeting, or exceeding Institute of Medicine recommendations. Hypertensive disorders of pregnancy included gestational hypertension, preeclampsia with or without severe features, superimposed preeclampsia, eclampsia, and HELLP syndrome.

Key findings

In the pregestational diabetes cohort, exposure to GLP-1 RA was not associated with gestational weight gain below or above recommendations. Any exposure was also not associated with hypertensive disorders of pregnancy after adjustment for prepregnancy body mass index, race and ethnicity, and chronic hypertension diagnosis (adjusted odds ratio [aOR], 0.72; 95% CI, 0.42-1.25).

In the weight-management cohort, any exposure was associated with lower odds of gestational weight gain below recommendations after adjustment for parity, hypertensive disorders of pregnancy, and polycystic ovarian syndrome diagnosis (aOR, 0.37; 95% CI, 0.18-0.78). When stratified by timing, exposure during pregnancy was associated with lower odds of gestational weight gain below recommendations (aOR, 0.29; 95% CI, 0.12-0.70), but prepregnancy-only exposure was not.

Exposure was not associated with gestational weight gain exceeding recommendations in the weight-management cohort (aOR, 1.29; 95% CI, 0.69-2.41).

For hypertensive disorders of pregnancy, any GLP-1 RA exposure was not associated with lower odds in the weight-management cohort after adjustment for parity, chronic hypertension diagnosis, gestational diabetes, preterm birth, polycystic ovarian syndrome diagnosis, and gestational weight gain (aOR, 0.83; 95% CI, 0.45-1.52).

Investigators noted that although the associations with hypertensive disorders of pregnancy were not statistically significant, the risk estimates showed a 28% reduction in the pregestational diabetes cohort and a 17% reduction in the weight-management cohort, warranting further study.

Clinical context

The authors wrote that the association between exposure and lower odds of gestational weight gain below recommendations in the weight-management cohort may reflect weight regain after stopping therapy when pregnancy is recognized or during pregnancy planning. They noted that prior nonpregnancy data have shown substantial weight regain after discontinuation of semaglutide, including regain of approximately two-thirds of weight lost within 1 year after treatment withdrawal.

The study did not establish safety of GLP-1 RAs during pregnancy. The authors noted that animal studies have raised concerns about embryonic death, growth restriction, and malformations, while human case reports of first-trimester exposure have not demonstrated those adverse offspring outcomes.

Study limitations included its retrospective observational design, potential residual confounding, small sample sizes, possible missed exposure from sources outside the electronic medical record, lack of data on glycemic control and medication-associated weight loss during pregnancy, and reliance on diagnosis codes for some variables.

The authors concluded that larger cohorts are needed to evaluate pregnancy safety and clarify whether early exposure could influence hypertensive disorders of pregnancy or gestational weight gain patterns.

Reference:

Pondugula N, Culhane JF, Lundsberg LS, Partridge C, Merriam AA. Gestational weight gain and hypertensive disorders of pregnancy with prepregnancy and early pregnancy glucagon-like peptide-1 receptor agonist exposure. Obstet Gynecol. 2026;147(3):293-302. doi:10.1097/AOG.0000000000005995