Hypertensive disorders of pregnancy and GLP-1 receptor agonist timing: a systematic review and meta-analysis.
Current evidence does not show a significant association between GLP-1 receptor agonist exposure and hypertensive disorders of pregnancy risk, but further research is needed.
Where it sits
this study against the rest of the lixisenatide corpusSummary and findings
This systematic review and meta-analysis assessed the association between GLP-1 receptor agonists exposure before or during early pregnancy and the risk of hypertensive disorders of pregnancy. It included three retrospective cohort studies with a total of 10,880 pregnancies. The pooled analysis found no statistically significant association between GLP-1 RAs and HDP risk.
Abstract
<h4>Purpose</h4>Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), used to treat type 2 diabetes and obesity, may improve metabolic health before conception. However, their association to hypertensive disorders of pregnancy (HDP) after periconceptional or early pregnancy exposure remains unknown.<h4>Methods</h4>We performed a meta-analysis to investigating association between GLP-1 RAs preconception or first trimester of gestation exposure and HDP risk. Cochrane Central Register of Controlled Trials databases, ClinicalTrials.gov, PubMed, Scopus, and EMBASE databases were searched from inception through December 15, 2025. All eligible studies were observational cohorts. Case reports, reviews, editorials, and studies that lacked HDP data were excluded. We pooled odds ratios with 95% confidence intervals using a random-effects Mantel-Haenszel model. ROBINS-I tool was used to evaluate risk of bias.<h4>Results</h4>Of 75 records identified, 3 retrospective cohort studies met inclusion criteria with 10,880 pregnancies (4942 exposed to GLP-1 RAs and 5938 unexposed). All the studies were conducted in the United States between 2014-2025 and evaluated the semaglutide, liraglutide, dulaglutide, tirzepatide, exenatide, lixisenatide, and albiglutide exposure. Two studies showed a lower HDP risks among exposed pregnant, whereas one study found a higher risk. In the pooled analysis, GLP-1 RA exposure showed a HDP risk with an OR 0.91 (OR 0.91, CI 0.57-1.47) with no statistical significance.<h4>Conclusion</h4>Periconceptional or first-trimester exposure to GLP-1 RAs are not significantly associated with HDP risk. This available evidence is limited and indicating the need for large prospective studies to establish a possible association between GLP-1 RAs are not significantly associated with HDP risk.
Background
Hypertensive disorders of pregnancy (HDP) are significant complications that can affect maternal and fetal outcomes. GLP-1 receptor agonists are primarily used for type 2 diabetes and obesity management, and their potential impact on HDP risk when used before or during early pregnancy is not well understood. This study aims to clarify whether exposure to GLP-1 RAs around conception or in the first trimester influences the risk of developing HDP.
Methods
This meta-analysis included observational cohort studies, excluding case reports, reviews, and studies without HDP data. A comprehensive search was conducted across several databases up to December 15, 2025. The included studies were retrospective cohorts from the United States, evaluating various GLP-1 RAs. The primary outcome was the risk of HDP, analyzed using a random-effects Mantel-Haenszel model to pool odds ratios.
Results
The meta-analysis included three studies with a total of 10,880 pregnancies, of which 4942 were exposed to GLP-1 RAs. The pooled odds ratio for HDP risk was 0.91 with a 95% confidence interval of 0.57 to 1.47, indicating no statistically significant association. The results varied among studies, with two reporting lower HDP risks and one reporting higher risk among exposed pregnancies.
Interpretation
The findings suggest no significant association between GLP-1 RA exposure and HDP risk, but the results are not definitive due to the limited number of studies and wide confidence intervals. The lack of statistical significance and the retrospective nature of the data limit the clinical implications. Larger, prospective studies are needed to better understand the potential impact of GLP-1 RAs on HDP risk.
Key findings
- 10,880 pregnancies analyzed (4942 exposed, 5938 unexposed).
- Pooled odds ratio for HDP risk with GLP-1 RA exposure: 0.91 (CI 0.57-1.47).
- No statistical significance in HDP risk reduction.
- Studies conducted in the United States between 2014-2025.
- Three retrospective cohort studies included.
Limitations
- Small number of included studies.
- Retrospective cohort design.
- Wide confidence intervals.
- Limited to studies conducted in the United States.
- Potential variability in GLP-1 RA formulations and dosages.