2149-P: The Association between GLP-1 and GIP Hormone Levels in Early Pregnancy and Subsequent Gestational Weight Gain

Introduction and Objective: Glucagon-like peptide receptor-1 (GLP-1) receptor agonists (RAs) and gastric inhibitory polypeptide (GIP) RAs are promising medications for the management of diabetes and obesity, especially among reproductive-age populations. Little is known about how levels of the incretin hormones that they mimic are associated with gestational weight gain (GWG). Our aim was to determine the association between GLP-1 and GIP hormone levels from early pregnancy and the risk of excessive GWG, with the hypothesis that higher levels would be associated with lowered risk. Methods: In a prospective cohort of women with a singleton birth (2014-2019) within KPNC (N = 748), blood samples were collected at 10-13 gestational weeks. Hormone levels were log-transformed and discretized into tertiles (T). Rate of GWG from the time of blood sample collection to delivery was categorized based on pre-pregnancy BMI per the 2010 National Academies of Medicine guidelines: inadequate, adequate, and excessive. We ran multinomial logistic regression to compare T2 or T3 of GIP-1 or GIP with T1, adjusting for age, education, insurance, parity, pre-pregnancy BMI, race and ethnicity, gestational age at blood collection. Results: The median level of GLP-1 was 3.9 pg/ml (IQR: 5.7), GIP was 26.6 pg/ml (SD: 82.5) and 52% of women had excessive GWG. As compared to the lowest GLP-1 tertile (T1), the odds ratio (OR) of excessive GWG decreased across tertiles and was statistically significant for T3: T2 0.77 (95% CI: 0.51-1.18), T3: 0.63 (0.41-0.97); p for trend=0.04. There was no association between GLP-1 tertiles and inadequate GWG [OR for T2 and T3 vs T1: 0.60 (0.32-1.14); and 0.99 (0.55-1.78), respectively]. There were no associations between GIP and excessive or inadequate GWG. Conclusion: Higher levels of GLP-1, but not GIP, are associated with lower risk of excessive GWG but not inadequate GWG. Future studies are warranted to assess the associations of incretin hormones in pregnancy with other perinatal outcomes and investigate the underlying physiological mechanisms to inform recommendations for GLP-1 RAs and GIP-RAs in reproductive-age populations. Disclosure S.S. Bane: None. A. Ferrara: None. J. Feng: None. Y. Zhu: None. M. Hedderson: None. Funding National Institutes of Health (UH3OD035540, UH3OD023289, R01ES019196)