Objective: The prevalence of type 2 diabetes (T2D) in pregnancy has tripled over the last two decades. Use of glucagon-like peptide-1 receptor agonists (GLP-1 RA) in pregnancy is contraindicated. Effects of pre-pregnancy GLP-1 RA use on pregnancy outcomes, including gestational weight gain (GWG), are poorly understood.

Methods: In a retrospective cohort of singleton pregnancies (2016 to 2022) in people with pre-existing T2D, we used propensity score matching on pre-pregnancy body mass index (BMI), maternal age, gestational age at delivery, race/ethnicity, and health insurance status to compare pregnancies with pre-pregnancy exposure to GLP-1 RA to unexposed pregnancies. We identified exposed pregnancies using prescription records and electronic chart searches. The primary outcome, GWG, was defined as the weight prior to delivery minus the pre-pregnancy weight, as documented in electronic medical record. A secondary outcome, excess GWG, was determined based on pre-pregnancy BMI, GWG, and clinical guidelines. We matched each GLP-1 RA exposed pregnancy to 3 unexposed pregnancies. We fit linear and logistic mixed models to evaluate associations between GLP-1 RA exposure and GWG.

Results: We included 188 pregnancies (47 exposed and 141 unexposed). Mean [SD] maternal age was 34.5 [5.3] years and mean [SD] pre-pregnancy BMI was 35.5 [7.6] kg/m2. GLP-1 RA exposed pregnancies had greater GWG (mean [SD]: 24.9 [12.0] lbs.) than unexposed pregnancies (19.1 [17.3] lbs., β= 5.9 lbs., 95% CI [0.60, 11.1], P=0.03). The proportion of pregnancies that exceeded recommended GWG was greater in GLP-1 RA-exposed than in unexposed pregnancies (61.7% vs 41.1%, P=0.02).

Conclusion: GWG in T2D-affected pregnancies with pre-pregnancy exposure to GLP-1 RA is greater than in matched pregnancies without pre-pregnancy GLP-1 RA exposure. Better understanding of the benefits and risks of pre-pregnancy use of GLP-1 RA is necessary to optimize care of T2D in pregnancy.

Disclosure

J. Maya: None. D. Pant: None. K. James: None. C. Michalopoulos: None. S. Hsu: None. L. Shook: None. T. Thaweethai: None. M. Hivert: None. C.E. Powe: Consultant; Mediflix. Other Relationship; Wolters Kluwer Health.

Funding

National Institutes of Health (T32DK007028-47S1)

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