In 3,652 women with type 2 diabetes, first-trimester GLP-1 receptor agonist exposure showed no increase in maternal mortality, pregnancy complications, or fetal heart and kidney anomalies compared to unexposed controls.
No increased risk across all outcomesIn 3,652 propensity-matched pregnancies, GLP-1RA exposure around the first trimester did not increase maternal mortality, preeclampsia, or fetal cardiac/kidney anomalies
What the researchers found
After propensity score matching of 3,652 first-trimester pregnant women with T2D (average age 36.2 years in the GLP-1RA group), maternal all-cause mortality was comparable between GLP-1RA-exposed and control cohorts at 42 weeks. Secondary maternal outcomes — gestational hypertension, preeclampsia, and eclampsia — were also comparable. Fetal cardiac and kidney anomaly risks were not increased in the GLP-1RA-exposed group. The analysis used a global EHR database of over 140 million patients.
Why it matters
GLP-1 receptor agonists are the fastest-growing drug class in medicine, increasingly used by women of reproductive age for both diabetes and weight management. The FDA recommends discontinuation at least 2 months before pregnancy due to animal data suggesting harm, but unplanned pregnancies inevitably expose some women during the first trimester. This is one of the largest studies to date examining what actually happens when this occurs, providing real-world safety data that has been urgently needed.
How the study worked
Retrospective propensity score-matched cohort study using a global electronic health records database (>140 million patients). 3,652 women with T2D were identified and divided into GLP-1RA-exposed (within 1 year before and 1 month after first-trimester pregnancy diagnosis) and unexposed cohorts. Propensity score matching controlled for confounders. Primary outcome was maternal all-cause mortality; secondary outcomes included pregnancy complications and fetal anomalies, with 42-week follow-up.
What this study cannot tell us
This is a retrospective observational study, not a randomized trial. EHR data may have coding errors, missing information, and surveillance bias. The study only examined outcomes through 42 weeks, not long-term child developmental outcomes. Rare adverse events may not be detectable even with 3,652 patients. The abstract appears truncated, suggesting possible reporting limitations. Exposure was defined broadly (within 1 year before and 1 month after pregnancy), so actual drug levels during organogenesis may vary significantly.
How to read the evidence
This is a large retrospective cohort study with propensity score matching from a global EHR database. While the sample size and matching methodology are strengths, the observational design cannot establish causation, and EHR data limitations affect completeness of outcome ascertainment.
When this study was published
Published in 2025, this study addresses one of the most timely safety questions in medicine as GLP-1 drug use among women of reproductive age continues to surge.
The bigger picture
The intersection of GLP-1 drugs and reproductive health is one of the most pressing pharmacovigilance questions in modern medicine. Media has reported 'Ozempic babies' — unexpected pregnancies in women on GLP-1 drugs — making pregnancy safety data essential. This study provides the first large-scale evidence that first-trimester exposure does not appear to increase major adverse maternal or fetal outcomes. However, it does not address long-term developmental outcomes or the full spectrum of birth defects, and should not change current guidelines recommending discontinuation before planned pregnancy.
Questions still open
- Are there developmental or neurobehavioral effects on children exposed to GLP-1RAs in utero that appear later in childhood?
- Does the timing of GLP-1RA discontinuation relative to conception affect outcomes?
- Should the 2-month pre-pregnancy washout recommendation for GLP-1RAs be revisited based on this data?
Common questions
Is it safe to take Ozempic or similar drugs during pregnancy?
Why are so many women getting pregnant while on GLP-1 drugs?
Read the original research
Efficacy and Safety of Glucagon-like Peptide-1 Receptor Agonist Use During the First Trimester in Pregnant Women With Type 2 Diabetes.
The American journal of cardiology, 246, 10-13
Citation
Hanif, Muhammad; Hays, Allison G; Nagarajan, Jai S; Sah, Shiva P; Weinstock, Ruth S; Taub, Cynthia C. (2025). Efficacy and Safety of Glucagon-like Peptide-1 Receptor Agonist Use During the First Trimester in Pregnant Women With Type 2 Diabetes.. The American journal of cardiology, 246, 10-13. https://doi.org/10.1016/j.amjcard.2025.03.013