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

Table 6 Mixed diabetes/obesity comparative cohorts and registry studies

Ref.	Country/design	Exposed population	GLP-1RA	Exposure window/cessation timing	Comparator	Maternal outcomes	Fetal/neonatal outcomes	Strength	Limitation	Interpretation
Hviid et al[39], 2026	Denmark; observational cohort	Liraglutide-exposed 295; semaglutide-exposed 234; T2D and obesity subgroups	Liraglutide and semaglutide vs unexposed	8 weeks before to 8 weeks after LMP	Unexposed to liraglutide, n = 756107; unexposed to semaglutide, n = 310825	Crude analyses-liraglutide: PET 9.2% vs 3.5%, P < 0.001. Preterm 12% vs 5%, P < 0.001; GDM 9.8% vs 4.3%, P < 0.001. Semaglutide: PET 10% vs 3.8%, P < 0.001; preterm 14% vs 5%, P < 0.001; GDM 8.1% vs 5.5%, P = 0.075. After propensity-score matching, the principal persistent association was preterm birth: Liraglutide aOR = 1.38 (95%CI: 1.01-1.90) and semaglutide aOR = 1.51 (95%CI: 1.06-2.14); this association was concentrated among women with pre-existing diabetes and was not observed in the obesity-only subgroup. Other crude differences were largely attenuated	Crude analyses-Liraglutide: LGA 18% vs 10%, P < 0.001. SGA 9.5% vs 10%, P = 0.80; placental weight increased, P < 0.001. Semaglutide: LGA 21% vs 10%, P < 0.001; SGA 11% vs 10%, P = 0.6; placental weight increased, P < 0.001	National data; agent-specific analyses; propensity matching	Confounding by indication; mixed T2D/obesity; crude risks attenuated after matching	Risk higher for preterm in T2D-exposed cohorts but not obese cohort; most other differences attenuated after propensity matching
Dao et al[34], 2024	Europe/Israel/United Kingdom; prospective cohort	168 exposed; obese 117, T2D 46	Liraglutide 99; semaglutide 51; dulaglutide 11; exenatide 7	147 women initiated GLP-1RA treatment before conception; treatment was stopped at a median GA of 5 weeks (IQR: 4-6; range: 2-40 weeks)	T2D unexposed, n = 156; obese unexposed, n = 163	Live birth 59% vs 69% in T2D and 63% in obese; pregnancy loss including spontaneous abortion/stillbirth 23% vs 26% in T2D and 29% in obese; elective termination 18% vs 6% in T2D and 8% in obese	Preterm 8% vs 15.1% in T2D and 14.5% in obese; LGA 17.7% vs 23.4% in T2D and 6% in obese; SGA 8% vs 8.1% in T2D and 14.5% in obese; CD 46.4% vs 49.6% in T2D and 44.4% in obese; MCM: 3/117 vs 3/128 in T2D and 5/127 in obese	Prospective teratology service data; two relevant comparator groups	Small sample; referral bias; higher elective termination; limited power	Reassuring for preterm risk; increased termination; LGA risk higher than obese comparator but comparable to T2D comparator
Kolding et al[35], 2025	Denmark; retrospective semaglutide cohort	32; 27 on Ozempic, 5 on Wegovy; 22 also used insulin	Semaglutide	First trimester; 17 stopped in first trimester, and 14 continued throughout pregnancy	Insulin-exposed pregnancies without semaglutide, n = 547; no registered semaglutide or insulin, n = 103843	Insulin comparator: Preterm 20% vs 23%, P = NS. Unexposed comparator: Preterm 20% vs 4.8%, P = 0.002	Insulin comparator: MCM 9.4% vs 13.9%, P = NS; SGA 0% vs 4.1%, P = NS; LGA 20.7% vs 42.4%, P = 0.02; RDS 10.3% vs 8.9%, P = NS; neonatal hypoglycemia 10.3% vs 17%, P = NS; neonatal jaundice 17.2% vs 20.7%, P = NS. Unexposed comparator: MCM 9.4% vs 7.7%, P = NS; SGA 0% vs 9.5%, P = NS; LGA 20.7% vs 4.2%, P = 0.001; RDS 10.3% vs 2.4%, P = 0.024; neonatal hypoglycemia 10.3% vs 1.4%, P = 0.006; neonatal jaundice 17.2% vs 5.9%, P = 0.017	Semaglutide-specific; two comparator groups	Very small exposed sample; high risk of bias; many on insulin; confounding by T2D severity	Apparent risk vs general/unexposed population but not vs insulin-treated T2D; comparator selection is critical
Imbroane et al[36], 2025	United States; retrospective cohort	4267; T2D 1604, obesity 3276	Not specified; 426 tirzepatide cohort compared with 426 GLP-1RA cohort	2 years before conception; sub-analysis 24 months, 12 months, 6 months and 3 months before conception	1433709 unexposed unmatched; 4267 after matching	GDM 15.2% vs 18%; HDP 19.9% vs 22.8%; both P < 0.05. Reduced risk of both GDM and HDP	Preterm 3% vs 4.4%; CD 17.6% vs 19.7%; both P < 0.05; reduced risk of preterm and CD	Very large dataset; matching; timing sub-analyses; tirzepatide subgroup	Primarily preconception exposure; possible healthy-user and weight-loss confounding	Suggests antecedent GLP-1RA use may reduce coded GDM/HDP/preterm/CD; tirzepatide associated with lower CD risk
Pondugula et al[37], 2026	United States; retrospective cohort, 10-year data	243 total; T2D: 94, T1D: 9, obese 143; before pregnancy 84, during pregnancy 159	Semaglutide 153; liraglutide 50; dulaglutide 27; tirzepatide 8	1 year before pregnancy to 90 days after conception	375 unexposed: T2D 170, T1D 5, obese 200	Lower odds of GWG below IOM recommendation with pregnancy exposure rather than before pregnancy. Obese cohort: GWG below IOM, 26% vs 38%; P < 0.01 but not significant in the diabetic cohort. Diabetic cohort: Preterm 28.4% vs 31.6%; HDP 38.8% vs 41.7%. Obese cohort: Preterm 13.6% vs 10%; HDP 19.3% vs 22%; GDM 16.4% vs 22.5%	Diabetic cohort: FGR 7.8% vs 8.6%; LGA 27% vs 32.8%; fetal death 3.9% vs 2.9%. Obese cohort: FGR 4.3% vs 6.5%; LGA 12.4% vs 11.5%; fetal death 2.9% vs 0.5%	Indication-stratified diabetic and obese cohorts; multiple agents	Small exposed sample; mixed T1D/T2D/obesity; low power for rare outcomes	No consistent significant adverse signal; GWG pattern hypothesis-generating; HDP findings require confirmation
Maya et al[38], 2025	United States; retrospective pooled obstetric cohort, 9-year data	655 total; GWG cohort 448; T2D 104, obese 344; obstetric cohort 566	Semaglutide 202; liraglutide 118; dulaglutide 92; tirzepatide 29; others 5. Obstetric data: Semaglutide 247, liraglutide 145, tirzepatide 41	3 years before conception to 90 days after conception; sub-analysis 0-6 months before conception, n = 220; 90 days after conception, n = 70; > 90 days after conception, n = 4	GWG analysis: 448 exposed vs 1344 matched unexposed; birthweight analysis: 442 vs 1326; obstetric outcome analysis: 566 vs 1698	GWG: 13.7 kg vs 10.5 kg, +3.26 kg, P < 0.001. GWG lower in liraglutide than semaglutide, +2.08 kg vs +3.72 kg. Preterm: 17% vs 13%; liraglutide 13% vs 12%, semaglutide 14% vs 12%. HDP: 46% vs 36%; liraglutide 42% vs 33%; semaglutide 51% vs 38%. GDM: 20% vs 15%; liraglutide 24% vs 15%, semaglutide 17% vs 16%	CD: 46.4% vs 47%; liraglutide 41.3% vs 44.8%; semaglutide 48.5% vs 46.5%. LGA and SGA comparable	Agent and timing sub-analyses; evaluates GWG after GLP-1RA exposure/discontinuation	Exposure window extends up to 3 years; weight regain and discontinuation confounding	Prior GLP-1RA discontinuation associated with higher GWG and selected obstetric signals; residual confounding and discontinuation rebound likely. GWG higher, especially semaglutide subgroup; HDP higher in semaglutide than liraglutide; GDM higher in liraglutide than semaglutide
Broe et al[40], 2025	Denmark; Danish population-based prescription safety-screening cohort	55 liraglutide-exposed live births	Liraglutide	0-30 days before to 91 days after LMP	Unexposed general population, n = 743276	NR	MCM aOR = 3.52, 95%CI: 1.59-7.82	National registry; liraglutide-specific	Screening study; live-birth-only outcome; small liraglutide sample; general-population comparator; incomplete disease-specific confounder control	Hypothesis-generating liraglutide signal requiring disease-specific validation; not definitive teratogenic evidence
Brown et al[41], 2026	United States; observational cohort	3572	Liraglutide 903; semaglutide 1644; tirzepatide 461; dulaglutide 417; exenatide 128; albiglutide 15; lixisenatide 4	90 days before conception to first trimester	Continuation of further GLP-1RA dispensing into first trimester (n = 1433) vs no further dispensing after LMP among women with pre-LMP GLP-1RA dispensing (n = 1086)	Maternal outcomes not primary	Non-live birth: aRR = 1.09 (95%CI: 0.98-1.23); spontaneous abortion: aRR = 0.99 (95%CI: 0.88-1.13); elective termination: aRR = 1.78 (95%CI: 1.29-2.60). Among linked live births, prevalence ratios were 1.29 (95%CI: 0.82-2.06) for SGA, 1.08 (95%CI: 0.84-1.40) for LGA, and 1.21 (95%CI: 0.83-1.82) for MCM	Large cohort; clinically relevant continuer vs non-continuer comparison	Confounding by reason for continuation, disease severity, pregnancy intention and counseling; maternal outcomes NR	Reassuring against large fetal structural signal from continued dispensing; elective termination increase was likely influenced by pregnancy recognition, counseling, exposure anxiety, or pregnancy intention; no evidence supporting intentional continuation

aOR: Adjusted odds ratio; aRR: Adjusted risk ratio; CD: Cesarean delivery; FGR: Fetal growth restriction; GA: Gestational age from last menstrual period; GDM: Gestational diabetes mellitus; GLP-1RA: Glucagon-like peptide-1 receptor agonist; GWG: Gestational weight gain; HDP: Hypertensive disorders of pregnancy; IOM: Institute of Medicine; IQR: Interquartile range; LGA: Large for gestational age; LMP: Last menstrual period; MCM: Major congenital malformation; NR: Not reported/not retrievable; NS: Not significant; PET: Preeclampsia; RDS: Respiratory distress syndrome; SGA: Small for gestational age; T1D: Type 1 diabetes; T2D: Type 2 diabetes; 95%CI: 95% confidence interval.