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
Marie-Claude Addor,
David Baud,
Maya Berlin,
Alice Panchaud,
Thierry Buclin,
François R Girardin,
Ursula Winterfeld,
Corinna Weber-Schoendorfer,
Orna Diav-Citrin,
Faiza Lamine,
Kim Dao,
Svetlana Shechtman,
Reem Hegla Murad,
Ariela Hazan,
Jonathan L Richardson,
Georgios Eleftheriou,
Valentin Rousson,
Leonore Diezi,
David Haefliger,
Ana Paula Simões-Wüst
Affiliations
Marie-Claude Addor
10 Department of Woman-Mother-Child, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
David Baud
11 Materno-Fetal and Obstetrics Research Unit, Department Woman-Mother-Child, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland
Maya Berlin
5 Clinical Pharmacology and Toxicology Unit, Drug Consultation Center, Zerifin TIS, affiliated with the Faculty of Medicine, Tel Aviv University, Shamir Medical Center Assaf Harofeh, Tzrifin, Central, Israel
Alice Panchaud
14 Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland
Thierry Buclin
1 Swiss Teratogen Information Service and Clinical Pharmacology Service, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland
François R Girardin
1 Swiss Teratogen Information Service and Clinical Pharmacology Service, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland
Ursula Winterfeld
1 Swiss Teratogen Information Service and Clinical Pharmacology Service, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland
Corinna Weber-Schoendorfer
3 Charité - Universitätsmedizin Berlin, Pharmakovigilanzzentrum Embryonaltoxikologie, Institut für Klinische Pharmakologie und Toxikologie, Berlin, Germany
Orna Diav-Citrin
2 The Israeli Teratology Information Service, Ministry of Health, Jerusalem, Israel
Faiza Lamine
12 Endocrinology, Diabetes and Metabolism Service, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
Kim Dao
1 Swiss Teratogen Information Service and Clinical Pharmacology Service, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland
Svetlana Shechtman
2 The Israeli Teratology Information Service, Ministry of Health, Jerusalem, Israel
Reem Hegla Murad
2 The Israeli Teratology Information Service, Ministry of Health, Jerusalem, Israel
Ariela Hazan
5 Clinical Pharmacology and Toxicology Unit, Drug Consultation Center, Zerifin TIS, affiliated with the Faculty of Medicine, Tel Aviv University, Shamir Medical Center Assaf Harofeh, Tzrifin, Central, Israel
Jonathan L Richardson
6 The UK Teratology Information Service, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
Georgios Eleftheriou
7 Poison Control Center, Hospital ASST Papa Giovanni XXIII, Bergamo, Italy
Valentin Rousson
8 Center for Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland
Leonore Diezi
1 Swiss Teratogen Information Service and Clinical Pharmacology Service, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland
David Haefliger
1 Swiss Teratogen Information Service and Clinical Pharmacology Service, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland
Ana Paula Simões-Wüst
9 Department of Obstetrics, University Hospital Zurich, University of Zurich, Zurich, Switzerland
Objectives Glucagon-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.Design This 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.Setting Data were collected from the databases of six Teratology Information Services.Participants This 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.Results Exposure 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.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.
