Postpartum Weight Retention after Glucagon-Like Peptide 1 Receptor Agonist Discontinuation for Pregnancy

Introduction and Objective: Discontinuation of glucagon-like peptide-1 receptor agonists (GLP1RAs) for pregnancy is associated with greater gestational weight gain. It is unclear how stopping GLP1RAs for pregnancy and restarting treatment after delivery impacts postpartum weight retention (PPWR). Methods: In a retrospective cohort (2016 to 2024), we used GLP1RA prescriptions to identify exposure from 3 years prior to 90 days after conception in full-term, singleton pregnancies. Using propensity score weighting to adjust for pre-pregnancy BMI, maternal age, race/ethnicity, health insurance, year/location of delivery, pre-existing diabetes, and chronic hypertension, we compared PPWR (12-month weight minus pre-pregnancy weight) in GLP1RA exposed and unexposed pregnancies to estimate the average treatment effect on the treated. In subgroup analyses, we examined PPWR separately in exposed pregnancies with and without reinitiation of treatment within 9 months after delivery compared to the same group of unexposed pregnancies. Results: In a cohort of 290 GLP1RA exposed and 93,567 unexposed pregnancies, there was no significant difference in PPWR (weighted mean (SD) PPWR 6.3 (21.4) vs 2.9 (22.6) lbs respectively, mean difference 3.40 [-0.37, 7.16], p= 0.08). In subgroup analyses, there was no difference in PPWR in those with prior GLP1RA use who restarted treatment within <9 months postpartum (n=132) compared to unexposed pregnancies (weighted mean PPWR 4.1 [22.7] and 3.2 [21.8] lbs, mean difference 1.34 [-3.63, 6.30], p= 0.6). There was greater PPWR in those who did not restart treatment (n=158) compared to unexposed pregnancies (weighted mean PPWR 10.2 [19.7] and 2.8 [22.7] lbs, mean difference 6.25 [1.23, 11.27], p= 0.02). Conclusion: There was no significant difference in PPWR overall in individuals exposed to GLP1RAs prior to pregnancy compared to unexposed propensity weighted controls. However, there was 6lb greater PPWR at 12 months among individuals who did not restart GLP1RAs after delivery. Disclosure: J. Maya: None. Y. Fu: None. D. Pant: None. K. James: None. S. Hsu: None. D.C. Soria: None. L. Shook: Research Support; Ended; Dexcom, Inc. Other - Royalty for authorship; Current; UpToDate. T. Thaweethai: None. C. Powe: Research Support; Current; Dexcom, Inc. Other - Associate Editor of Diabetes Care, Honoraria for Educational Materials; Current; American Diabetes Association. Other - Royalties for Up To Date chapters; Current; Wolters Kluwer (Up To Date). Other - Speaker; Ended; Medscape. Funding: American Diabetes Association (9-24-JDFWH-01), MGH Physician/Scientist Development Award, National Institute of Health (5U24DK132733-04)