Journal Article

Use of GLP1 receptor agonists in early pregnancy and reproductive safety: a multicentre, observational, prospective cohort study based on the databases of six Teratology Information Services

Diezi, Leonore, Weber-Schoendorfer, Corinna, Hazan, Ariela, Addor, Marie-Claude, Shechtman, Svetlana, Murad, Reem Hegla, Eleftheriou, Georgios, Simões-Wüst, Ana Paula, Girardin, François R, Diav-Citrin, Orna, Haefliger, David, Winterfeld, Ursula, Rousson, Valentin, Berlin, Maya, Baud, David, Lamine, Faiza, Panchaud, Alice, Dao, Kim, Richardson, Jonathan L, Buclin, Thierry

2024

Overview

ObjectivesGlucagon-like peptide 1 receptor agonists (GLP1-RA) are indicated for the treatment of type 2 diabetes and more recently for weight loss. The aim of this study was to assess the risks associated with GLP1-RA exposure during early pregnancy.DesignThis multicentre, observational prospective cohort study compared pregnancy outcomes in women exposed to GLP1-RA in early pregnancy either for diabetes or obesity treatment with those in two reference groups: (1) women with diabetes exposed to at least one non-GLP1-RA antidiabetic drug during the first trimester and (2) a reference group of overweight/obese women without diabetes, between 2009 and 2022.SettingData were collected from the databases of six Teratology Information Services.ParticipantsThis study included 168 pregnancies of women exposed to GLP1-RA during the first trimester, alongside a reference group of 156 pregnancies of women with diabetes and 163 pregnancies of overweight/obese women.ResultsExposure to GLP1-RA in the first trimester was not associated with a risk of major birth defects when compared with diabetes (2.6% vs 2.3%; adjusted OR, 0.98 (95% CI, 0.16 to 5.82)) or to overweight/obese (2.6% vs 3.9%; adjusted OR 0.54 (0.11 to 2.75)). For the GLP1-RA group, cumulative incidence for live births, pregnancy losses and pregnancy terminations was 59%, 23% and 18%, respectively. In the diabetes reference group, corresponding estimates were 69%, 26% and 6%, while in the overweight/obese reference group, they were 63%, 29% and 8%, respectively. Cox proportional cause-specific hazard models indicated no increased risk of pregnancy losses in the GLP1-RA versus the diabetes and the overweight/obese reference groups, in both crude and adjusted analyses.ConclusionsThis study offers reassurance in cases of inadvertent exposure to GLP1-RA during the first trimester of pregnancy. Due to the limited sample size, larger studies are required to validate these findings.

• Publisher: British Medical Journal Publishing Group,BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Abnormalities, Drug-Induced - epidemiology / Adult / Birth defects / Birth weight / Body mass index / Cohort analysis / Data collection / Databases, Factual / Diabetes / Diabetes in pregnancy / Diabetes Mellitus, Type 2 - drug therapy / Drug dosages / Female / Gestational age / GLP-1 receptor agonists / Glucagon / Glucagon-Like Peptide-1 Receptor - agonists / Humans / Hypoglycemic Agents - adverse effects / Hypoglycemic Agents - therapeutic use / Information services / Obesity / Obesity - epidemiology / Overweight / Patients / Peptides / Pharmacology and Therapeutics / Pregnancy / Pregnancy Complications - drug therapy / Pregnancy in Diabetics - drug therapy / Pregnancy Outcome - epidemiology / Pregnancy Trimester, First / Pregnant Women / Prospective Studies / Questionnaires / Safety / Weight control / Womens health