(308) Reproductive safety of glucagon-like peptide 1 receptor agonists (GLP1-RA) after maternal exposure in early pregnancy: a comparative ENTIS cohort study

Tuesday, August 27, 2024

8:00 AM – 6:00 PM CEST

Location: Convention Hall II

Co-Author(s)

KD

Kim Dao

Swiss Teratogen Information Service and Clinical Pharmacology Service, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland, Switzerland
SS

Svetlana Shechtman

The Israeli Teratology Information Service, Ministry of Health, Jerusalem, Israel, Israel
CW

Corinna Weber-Schoendorfer

Charité - Universitätsmedizin Berlin, Pharmakovigilanzzentrum Embryonaltoxikologie, Institut für Klinische Pharmakologie und Toxikologie, Berlin, Germany, Germany
OD

Orna Diav-Citrin

The Israeli Teratology Information Service, Ministry of Health, Jerusalem, Israel; The Hebrew University and Hadassah Medical School, Jerusalem, Israel, Israel
RH

Reem Hegla Murad

The Israeli Teratology Information Service, Ministry of Health, Jerusalem, Israel, Israel
MB

Maya Berlin

Clinical Pharmacology and Toxicology Unit, Drug Consultation Center, Shamir Medical Center (Assaf Harofeh), Zerifin TIS, affiliated with the Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, Israel
AH

Ariela Hazan

Clinical Pharmacology and Toxicology Unit, Drug Consultation Center, Shamir Medical Center (Assaf Harofeh), Zerifin TIS, affiliated with the Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, Israel
JR

Jonathan Luke Richardson

The UK Teratology Information Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK, United Kingdom
GE

Georgios Eleftheriou

Poison Control Center, Hospital ASST Papa Giovanni XXIII, Bergamo, Italy, Italy
VR

Valentin Rousson

Center for Primary Care and Public Health, University of Lausanne, Switzerland, Switzerland
LD

Leonore Diezi

Swiss Teratogen Information Service and Clinical Pharmacology Service, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland, Switzerland
DH

David Haefliger

Swiss Teratogen Information Service and Clinical Pharmacology Service, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland, Switzerland
AS

Ana Paula Simoes-Wüst

Department of Obstetrics, University Hospital Zurich, University of Zurich, Switzerland, Switzerland
MA

Marie-Claude Addor

Department of Woman-Mother-Child, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland, Switzerland
DB

David Baud

Materno-Fetal and Obstetrics Research Unit, Department Woman-Mother-Child, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland, Switzerland
FL

Faiza Lamine

Endocrinology, Diabetes and Metabolism Service. Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. Endocrinology and Diabetes Unit. Internal Medicine Service. Hôpital Riviera Chablais, Rennaz, Switzerland., Switzerland
AP

Alice Panchaud

Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland; Service of Pharmacy, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland, Switzerland
TB

Thierry Buclin

Swiss Teratogen Information Service and Clinical Pharmacology Service, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland, Switzerland
FG

François Girardin

Swiss Teratogen Information Service and Clinical Pharmacology Service, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland, Switzerland

Presenting Author(s)

Ursula Winterfeld, PhD

Head
Swiss Teratogen Information Service and Clinical Pharmacology Service, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland, Switzerland

Background: Glucagon-like peptide 1 receptor agonists (GLP1-RA) are widely used for the treatment of type 2 diabetes and for weight loss in women of childbearing age.

Objectives: The aim of this study was to assess the risks associated with GLP1-RA exposure during early pregnancy.

Methods:

Design: This multicentre, observational prospective cohort study compared pregnancy outcomes in women exposed to a GLP1-RA in early pregnancy either for diabetes or obesity treatment with those in two reference groups: (i) of diabetic women exposed to at least one non-GLP1-RA antidiabetic drug during the first trimester and (ii) a reference group of overweight/obese women without diabetes, between 2009 and 2022.
Setting: Data were collected from the databases of six Teratology Information Services.
Participants: This study included 168 pregnancies of women exposed to a GLP1-RA during the first trimester, alongside a reference group of 156 pregnancies of women with diabetes and 163 pregnancies of overweight/obese women. To assess the association between GLP1-RA exposure and the risk of major birth defects, multivariate logistic regression analysis was conducted, generating an unadjusted and an adjusted odds ratio (OR) with a corresponding 95% confidence interval (CI). To assess the association between exposure and the overall risk of pregnancy loss, cause-specific Cox proportional hazards models were used, considering any variation in gestational age at enrolment across the three groups. In the hazard models, adjustment was performed for various confounding factors.

Results: Exposure to a GLP1-RA in the first trimester was not associated with a risk of major birth defects when compared to diabetes (2.6% versus 2.3%; adjusted odds ratio (OR) [95% confidence interval], 0.98 [0.16–5.82]) or to overweight/obese (2.6% versus 3.9%; adjusted OR 0.54 [0.11–2.75]). 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%. Cox proportional cause-specific hazards 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.

Conclusions: This 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.