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

BMJ Open. 2024 Apr 24;14(4):e083550. doi: 10.1136/bmjopen-2023-083550.

Abstract

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.

Keywords: Diabetes in pregnancy; Obesity; Pregnant Women; Safety.

Publication types

  • Observational Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Drug-Induced / epidemiology
  • Adult
  • Databases, Factual
  • Diabetes Mellitus, Type 2 / drug therapy
  • Female
  • Glucagon-Like Peptide-1 Receptor* / agonists
  • Humans
  • Hypoglycemic Agents* / adverse effects
  • Hypoglycemic Agents* / therapeutic use
  • Obesity* / epidemiology
  • Pregnancy
  • Pregnancy Complications / drug therapy
  • Pregnancy Outcome* / epidemiology
  • Pregnancy Trimester, First*
  • Pregnancy in Diabetics / drug therapy
  • Prospective Studies

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents