Pregnancy and perinatal outcomes following exposure to GLP-1 and dual GLP-1/GIP receptor agonists: a time-window-stratified systematic review and meta-analysis
- 1Department of Obstetrics and Gynecology, MegaPoint Hospital
- 2Department of Medical Pharmacology, Faculty of Medicine, Kahramanmaraş Sütçü İmam University
Abstract
Background: To evaluate maternal, fetal, and neonatal outcomes after preconception or gestational exposure to glucagon-like peptide-1 receptor agonists and dual glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptor agonists, and to assess the reproducibility of reported safety signals.
Methods: Six databases plus a drug-level safety search were searched through 16 July 2026. Exposure was classified into four clinically defined time windows. Independent studies or data sources were the analytic unit; one primary comparator was selected per study, and odds ratios and risk ratios were synthesized separately. Random-effects meta-analysis, timing-stratified and dominant-study sensitivity analyses, Newcastle-Ottawa Scale assessment, and GRADE certainty assessment were used.
Results: Fourteen comparative data sources were included; 13 were quantitatively eligible and eight contributed to at least one pooled estimate. In the timing-specific analysis of major congenital malformations, four studies with verified periconceptional/first-trimester exposure yielded an odds ratio of 0.99 (95% confidence interval 0.77–1.27). A secondary pregnancy-period analysis that added one unadjusted, trimester-unspecified cohort yielded 1.00 (0.94–1.06); that cohort contributed 93.5% of the weight. Pooled preterm birth, small-for-gestational-age birth, and stillbirth analyses showed no statistically significant differences. Preeclampsia and other sparse outcomes were not pooled. Certainty was very low for all key outcomes.
Conclusion: Current evidence does not demonstrate a clear or consistent increase in major congenital malformation risk, but very low certainty, imprecision, residual confounding, heterogeneous comparators, sparse agent-specific data, and uncertain exposure timing preclude conclusions of safety. Reported preeclampsia and renal or urinary signals have not been independently replicated.
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BibTeX
@article{mavigok2026pregnancy,
title = {{Pregnancy and perinatal outcomes following exposure to GLP-1 and dual GLP-1/GIP receptor agonists: a time-window-stratified systematic review and meta-analysis}},
author = {Erkan Mavigök and Ayşe Nur Mavigök},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1994366},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1994366/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Pregnancy and perinatal outcomes following exposure to GLP-1 and dual GLP-1/GIP receptor agonists: a time-window-stratified systematic review and meta-analysis
AU - Erkan Mavigök
AU - Ayşe Nur Mavigök
PY - 2026
DA - 2026/10/16
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1994366
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1994366/full
AB - Background: To evaluate maternal, fetal, and neonatal outcomes after preconception or gestational exposure to glucagon-like peptide-1 receptor agonists and dual glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptor agonists, and to assess the reproducibility of reported safety signals. Methods: Six databases plus a drug-level safety search were searched through 16 July 2026. Exposure was classified into four clinically defined time windows. Independent studies or data sources were the analytic unit; one primary comparator was selected per study, and odds ratios and risk ratios were synthesized separately. Random-effects meta-analysis, timing-stratified and dominant-study sensitivity analyses, Newcastle-Ottawa Scale assessment, and GRADE certainty assessment were used. Results: Fourteen comparative data sources were included; 13 were quantitatively eligible and eight contributed to at least one pooled estimate. In the timing-specific analysis of major congenital malformations, four studies with verified periconceptional/first-trimester exposure yielded an odds ratio of 0.99 (95% confidence interval 0.77–1.27). A secondary pregnancy-period analysis that added one unadjusted, trimester-unspecified cohort yielded 1.00 (0.94–1.06); that cohort contributed 93.5% of the weight. Pooled preterm birth, small-for-gestational-age birth, and stillbirth analyses showed no statistically significant differences. Preeclampsia and other sparse outcomes were not pooled. Certainty was very low for all key outcomes. Conclusion: Current evidence does not demonstrate a clear or consistent increase in major congenital malformation risk, but very low certainty, imprecision, residual confounding, heterogeneous comparators, sparse agent-specific data, and uncertain exposure timing preclude conclusions of safety. Reported preeclampsia and renal or urinary signals have not been independently replicated.
SN - 1663-9812
ER -