Human pregnancy outcomes after early glucagon-like peptide-1 receptor agonist exposure: A scoping review

Table 7 Systematic reviews and meta-analyses of human glucagon-like peptide-1 receptor agonist exposure around pregnancy

Ref.	Search window/databases	Included evidence	Exposed pregnancies	Exposure window	Main maternal outcomes	Main fetal/neonatal outcomes	Strength	Limitation	Interpretation
Kodali et al[42], 2026	PubMed and Google Scholar; January 2010-April 2025	4 observational studies: 3 retrospective cohorts from North America/Europe and 1 prospective cohort from Europe/Middle East	5405 exposed for fetal composite analysis; total pregnancies 36963	During or before pregnancy; only 21% periconceptional/first trimester	Adverse maternal outcomes lower: OR = 0.72, 95%CI: 0.66-0.79, P < 0.00001. Preterm birth lower: OR = 0.66, 95%CI: 0.53-0.82, P = 0.0001	Major congenital anomalies not increased: OR = 1.08, 95%CI: 0.86-1.37, P = 0.51; insulin-only comparator OR = 1.00, 95%CI: 0.77-1.28, P = 0.98. Overall adverse fetal outcomes: Text reports OR = 0.91, 95%CI: 0.72-1.16, P = 0.44; forest plot reports OR = 0.59, 95%CI: 0.36-0.96, P = 0.03 with I2 = 87%	Focused SRMA; includes comparator cohorts; highlights lack of MCM signal	Only 4 studies; no formal risk-of-bias table reported; text/figure inconsistency for adverse fetal outcome; sparse outcomes; study dominance; heterogeneous exposure/comparators	Reassuring for MCM, but apparent maternal/preterm benefit should be interpreted as observational association rather than drug benefit
Armstrong et al[43], 2025	PubMed, EMBASE, Cochrane; up to June 2025	Comparative studies; table/review reports inconsistently describe 6-9 studies; includes cohort/RCT-derived data	8761 exposed among 182269 participants	Pregnancy/preconception; first-trimester subgroup reported	GDM: OR = 0.86, 95%CI: 0.56-1.32, P = 0.49. Miscarriage: OR = 1.16, 95%CI: 0.82-1.65, P = 0.41. Live birth: OR = 0.72, 95%CI: 0.50-1.06, P = 0.10	Major birth defects: OR = 0.97, 95%CI: 0.77-1.22, P = 0.79; CHD: OR = 0.63, 95%CI: 0.42-0.95, P = 0.03; preterm delivery: OR = 1.66, 95%CI: 0.23-12.23, P = 0.62, I2 = 98%; stillbirth: OR = 0.29, 95%CI: 0.07-1.20, P = 0.09	Used ROBINS-I/RoB2; leave-one-out sensitivity; first-trimester subgroup analyses; publication bias not assessed because fewer than 10 studies	Internal inconsistency in study count; pooled heterogeneous evidence including Parker regulatory data and preconception fertility RCT; high heterogeneity for preterm birth; unexpected protective CHD signal likely confounded	Supports absence of major malformation signal; not sufficient to infer fetal protection or pregnancy safety
Hakim et al[44], 2026	PubMed, EMBASE, Web of Science; through Nov 2025	22 studies in systematic review; 10 comparative observational studies in meta-analysis; case reports/series and pharmacovigilance summarized narratively	49395 exposed pregnancies overall; 43579 exposed in comparative observational MA as reported	3 months before LMP through pregnancy	Preterm delivery OR = 1.11, 95%CI: 0.84-1.47, I2 = 46.1%; live birth OR = 0.63, 95%CI: 0.37-1.09; spontaneous pregnancy loss OR = 1.13, 95%CI: 0.68-1.88; elective termination OR = 2.39, 95%CI: 0.32-17.68; HDP OR = 0.86, 95%CI: 0.52-1.43; preeclampsia OR = 1.55, 95%CI: 0.57-4.19; CD OR = 1.42, 95%CI: 0.55-3.64	MCM: OR = 1.19, 95%CI: 0.72-1.98, I2 = 58.5%; CHD: OR = 0.88, 95%CI: 0.53-1.44, I2 = 47.7%; renal malformations OR = 1.23, 95%CI: 1.09-1.39, I2 = 0%, largely driven by one large cohort; T2D-only MCM: OR = 1.01, 95%CI: 0.98-1.06; semaglutide-only live birth: OR = 0.57, 95%CI: 0.35-0.95	Largest and most comprehensive synthesis; separates comparative MA from narrative noncomparative evidence; comparator-specific and agent-specific analyses; Joanna Briggs Institute appraisal	Residual confounding by disease severity; prescription/dispensing exposure misclassification; heterogeneous comparators; publication-bias assessment was limited by the small number of studies contributing to individual outcomes; no clear leave-one-out for renal signal	Strongest current synthesis: Cautiously reassuring for overall MCM, but renal signal and semaglutide live-birth finding require cautious, granular evaluation

A Measurement Tool to Assess Systematic Reviews-2 critical-domain appraisal of the included systematic reviews and meta-analyses is provided in Supplementary Table 7. CD: Cesarean delivery; CHD: Congenital heart disease; GDM: Gestational diabetes mellitus; HDP: Hypertensive disorders of pregnancy; LMP: Last menstrual period; MA: Meta-analysis; MCM: Major congenital malformation; OR: Odds ratio; RCT: Randomized controlled trial; RoB: Risk of bias; ROBINS: Risk of bias in non-randomized studies of interventions; SRMA: Systematic review and meta-analysis; T2D: Type 2 diabetes; 95%CI: 95% confidence interval.