Efficacy and Safety of Glucagon-like Peptide-1 Receptor Agonist Use During the First Trimester in Pregnant Women With Type 2 Diabetes

Am J Cardiol. 2025 Jul 1:246:10-13. doi: 10.1016/j.amjcard.2025.03.013. Epub 2025 Mar 17.

Abstract

Background: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are a newer class of antidiabetic drugs that have proven beneficial in reducing weight loss and improving cardiometabolic profile. Literature has shown worsened glycemic control and increased risk of cardiovascular outcomes after stopping GLP-1 RAs in the adult type 2 diabetes (T2D) population; however, the effect of exposure to GLP-1 RAs in first-trimester pregnancy, followed by discontinuation, is still unclear.

Objective: To evaluate the maternal and fetal clinical outcomes after exposure of GLP-1 RAs in a T2D first-trimester pregnant population.

Methods: This retrospective cohort was based on a global database of electronic health records (EHRs) of more than 140 million patients. After propensity score matching (PSM), the study population included 3,652 women with T2D, divided into 2 cohorts based on their exposure to GLP-1 RAs within 1 year before and 1 month after diagnosis of first-trimester pregnancy. Exposure to GLP-1 RAs within 1 year before and 1 month after diagnosis of first-trimester pregnancy in T2D women.

Results: In this study of a 3,652 first-trimester T2D population, the average age of the GLP-1 RAs exposed cohort was 36.2 years. The primary outcome of the maternal all-cause mortality rate was comparable in the GLP-1 RAs-exposed first-trimester pregnant cohort compared to the control cohort after 42 weeks of follow-up. Secondary maternal outcomes, i.e., gestational hypertension, preeclampsia, and eclampsia, were also comparable after 42 weeks of follow-up in the women with T2D exposed to GLP-1 RAs during their pregnancy as compared to the control. Similarly, the relative risk of fetal cardiac and kidney anomalies was comparable between the cohorts.

Conclusion: In this study, exposure to GLP-1 RAs during the first trimester of pregnancy in T2D.

Keywords: and eclampsia; fetal anomalies; first trimester pregnancy; gestational hypertension; glucagon like receptor-I receptor agonists; preeclampsia; type-ii diabetes mellitus.

MeSH terms

  • Adult
  • Diabetes Mellitus, Type 2* / drug therapy
  • Female
  • Glucagon-Like Peptide-1 Receptor Agonists*
  • Humans
  • Hypoglycemic Agents* / therapeutic use
  • Pregnancy
  • Pregnancy Outcome
  • Pregnancy Trimester, First
  • Pregnancy in Diabetics* / drug therapy
  • Retrospective Studies

Substances

  • Glucagon-Like Peptide-1 Receptor Agonists
  • Hypoglycemic Agents