Hypertensive disorders of pregnancy and GLP-1 receptor agonist timing: a systematic review and meta-analysis

Exposure to GLP-1 receptor agonists around conception or in the first trimester was not significantly associated with hypertensive disorders of pregnancy in a pooled analysis of three retrospective cohort studies. The meta-analysis found an odds ratio of 0.91 with a wide confidence interval crossing 1. The authors note the evidence is limited and call for larger prospective studies.

Meta-analysis — meta-analysis of retrospective cohort studies. Population: pregnancies exposed to GLP-1 RAs periconceptionally or in the first trimester, assessed for hypertensive disorders. Sample size: 10,880 pregnancies. Interventions: semaglutide; liraglutide; dulaglutide; tirzepatide; exenatide; lixisenatide; albiglutide.

Of 75 records identified, 3 retrospective cohort studies met inclusion criteria. The pooled OR for HDP with GLP-1 RA exposure was 0.91 (95% CI 0.57-1.47), indicating no statistically significant association. Two studies found lower HDP risk among exposed pregnancies, while one found higher risk. The analysis included 10,880 pregnancies (4,942 exposed, 5,938 unexposed).

For researchers studying liraglutide, this paper places it among a class of GLP-1 RAs evaluated for HDP risk in early pregnancy. It does not establish a statistically significant association, but it also does not establish safety due to limited observational evidence.

Key findings

• Pooled analysis of 3 retrospective cohort studies found no significant association between GLP-1 RA exposure and HDP risk (OR 0.91, 95% CI 0.57-1.47).
• The three studies included 10,880 pregnancies, with 4,942 exposed to GLP-1 RAs and 5,938 unexposed.
• Two studies reported lower HDP risk in exposed pregnancies, while one study reported higher risk.
• All studies were conducted in the United States between 2014 and 2025.
• Evaluated agents included semaglutide, liraglutide, dulaglutide, tirzepatide, exenatide, lixisenatide, and albiglutide.

Limitations

• Authors state the available evidence is limited and call for large prospective studies.
• All included studies were observational retrospective cohorts, so confounding is possible.
• Only three studies met inclusion criteria, limiting precision and generalizability.

The record

• Journal: Endocrine 91(1): 241
• Published: 2026-07-31
• PMID: 42536323 — DOI: 10.1007/s12020-026-04701-9
• MeSH terms: Humans, Hypertension, Pregnancy-Induced, Hypoglycemic Agents, Pregnancy, Pregnancy Trimester, First, Female, Glucagon-Like Peptides, Liraglutide, Exenatide, Glucagon-Like Peptide-1 Receptor Agonists, Tirzepatide, Semaglutide
• Author countries: Czech Republic, Italy

Peptide profiles: Liraglutide.

All indexed evidence: Liraglutide trials & papers.

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