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

Table 1 Case reports of human glucagon-like peptide-1 receptor agonist exposure before or during pregnancy

Ref.	Country	GLP-1RA/dose	Exposure window/cessation timing	Maternal background/metabolic profile	Delivery/birth weight	Maternal outcome	Fetal/neonatal outcome	Follow-up	Interpretation
Williams et al[4], 2009	United States	Exenatide, dose NR	7 months preconception to 14 GW	35 years; T2D, HTN, obesity, proliferative retinopathy, microalbuminuria; HbA1c 10.4%	LUCS, 38 weeks; 2835 g	Preeclampsia, intra-amniotic infection, postpartum uterine infection	Low Apgar, mild encephalopathy, neonatal sepsis	3 months, uneventful	High-risk diabetes background; adverse neonatal outcome not clearly attributable to exenatide
Greco[5], 2015	Italy	Liraglutide 1.8 mg/day	2 years preconception to 12 GW	37 years; T2D for 5 years, obesity, PCOS, infertility; BMI: 32.2 kg/m2	LUCS, 37 weeks; 3790 g	Uneventful	Normal Apgar score; transient neonatal hypoglycemia	NR	Reassuring early liraglutide exposure; neonatal hypoglycemia likely diabetes-related
Ivanišević et al[6], 2018	Croatia	Liraglutide 1.8 mg/day	Preconception to throughout pregnancy and lactation	28 years; thyroidectomy for diffuse goiter/thyroid disease; uncontrolled T2D	LUCS, 39 weeks; 4220 g	Uneventful	Apgar 10/10; macrosomia	2 years, uneventful	Unique prolonged exposure/Lactation case; macrosomia likely related to diabetes
Livadas et al[7], 2020	Greece	Liraglutide 1.8 mg/day	14 weeks preconception to 6-7 GW	29 years; obesity with HAIR-AN syndrome, hirsutism, insulin resistance, acanthosis nigricans, severe PCOS	NR	Uneventful	Healthy baby	Uneventful	Reassuring inadvertent early exposure in severe PCOS/insulin-resistance phenotype
Burlina et al[8], 2023	Italy	Dulaglutide 1.5 mg/week	6 weeks preconception to 15 GW	38 years; T2D for 11 years, obesity	LUCS, 37 weeks; 2860 g	Gestational hypertension; 15 kg weight gain	Cavum septum pellucidum at 20 weeks, resolved; neonatal jaundice	NR	No persistent structural anomaly; maternal metabolic risk remains major confounder
Alghamdi et al[9], 2023	Saudi Arabia	Dulaglutide 1.5 mg/week	Preconception to 13 GW	39 years; T2D for 19 years, obesity	LUCS, 38 weeks; 3100 g	Uneventful	Mild bilateral pyelectasis; Down syndrome excluded	NR; unplanned pregnancy	Mild urinary finding; no clear teratogenic pattern
Skov et al[10], 2023	Denmark	Semaglutide 1 mg/week	7 months preconception to 4 GW	31 years; PCOS, uncomplicated myxedema	Vaginal delivery, 41 weeks + 5 days; 5230 g	35 kg gestational weight gain	Macrosomia, shoulder dystocia, neonatal hypoglycemia	6 months	Reassuring for malformation; macrosomia, shoulder dystocia, and neonatal hypoglycemia occurred in the setting of marked gestational weight gain and maternal metabolic risk
Wajtryt and Dedecjus[11], 2023	Poland	Semaglutide, dose NR	5 months preconception to 7 GW	43 years; T2D; G5P4	LUCS at term; 2750 g	Uneventful	None	NR	Reassuring but limited by sparse details
Patel and Healy[12], 2024	United States	Dulaglutide 0.75 mg/week	Preconception to 15 GW	41 years; T2D, PCOS, obesity	LUCS, 36 weeks; birth weight NR	Preeclampsia, preterm delivery	Polyhydramnios at 26 weeks, corrected by 32 weeks	NR	Maternal and fetal findings consistent with high-risk metabolic pregnancy
Molteni et al[13], 2024	Italy	Dulaglutide 1.5 mg/week	3 months preconception to 34 GW; continued during pregnancy	42 years; G6P5; T2D for 11 years; obesity, dyslipidemia	LUCS, 38 weeks, breech; 3790 g	5 kg weight gain; gestational hypertension	Polyhydramnios; fetal growth normal	NR	Important prolonged dulaglutide exposure; no malformation, but maternal HTN/polyhydramnios occurred
Okeke et al[14], 2024	United States	Semaglutide 2 mg, single self-administered dose	Before pregnancy recognition; pregnancy detected at 6-7 GW	34 years; G5P4; generalized anxiety, borderline personality, off-label weight loss, one previous preterm birth, three previous abortions	NR	NR	Hyperemesis gravidarum reported	NR	Limited interpretability; single-dose exposure and major psychiatric/obstetric background
Zhu et al[15], 2024	China	Semaglutide, dose NR	Before pregnancy to 6 GW	34 years; obesity	LUCS, 37 weeks; birth weight NR	NR	Micropenis, mild foot deformity	6 months, normal growth	Isolated anomaly report; no causal inference possible
Abushanab et al[16], 2025	Qatar	Liraglutide 3 mg/day	8 months preconception to 7 GW	29 years; G9P6; obesity, BMI 36 kg/m2; two previous preterm births, two abortions, four live births	LUCS, 37 weeks; 2330 g	Maternal weight gain 51 kg, from 80 kg to 131 kg	Low birth weight; Apgar 9/10	2 years, normal growth and neurodevelopment	Reassuring developmental follow-up; maternal weight rebound notable
Burlina et al[17], 2026	Italy	Dulaglutide, dose NR	Preconception to 23 GW	44 years; uncontrolled T2D	Vaginal delivery, birth weight 3025 g	Maternal weight gain 9 kg	No obstetric complications or congenital anomalies reported	NR	Prolonged exposure; reassuring but no follow-up
Huang et al[18], 2025	United States	Dulaglutide, dose NR	First-trimester exposure; exact GW NR	35 years; T2D, HTN, hyperlipidemia	NR	Hospitalized for septic arthritis of left shoulder with euglycemic DKA	Elective termination	NR	Termination and severe maternal illness confound fetal inference
Ozdemir[19], 2025	Greece	Liraglutide	Preconception to 3.5 GW	20 years; obesity	LUCS, 34 weeks; 2700 g	Developed GDM	NICU for 1 week	6 months, normal development	Early exposure; prematurity/GDM not clearly drug-related
Jin et al[20], 2026	China	Semaglutide 0.5 mg/week, off-label obesity use	6 months preconception to 7 GW	37 years; overweight, BMI: 27.73 kg/m2; chronic simple lichen planus; hypothyroidism	Vaginal delivery, 39.6 weeks; 3200 g	22 kg gestational weight gain; no GDM; no HTN or preeclampsia	Apgar 8/10 at 1 min, 10/10 at 5 min; fetal growth, NT and Doppler normal; healthy baby	3 months, uneventful	Reassuring early semaglutide exposure; GDM/weight gain remain important

Detailed Joanna Briggs Institute domain-level appraisal of case reports is provided in Supplementary Table 2. BMI: Body mass index; DKA: Diabetic ketoacidosis; G: Gravida; GDM: Gestational diabetes mellitus; GLP-1RA: Glucagon-like peptide-1 receptor agonist; GW: Gestational week; HAIR-AN: Hirsutism-insulin resistance-acanthosis nigricans; HbA1c: Glycated hemoglobin; HTN: Hypertension; LUCS: Lower uterine cesarean section; NICU: Neonatal intensive care unit; NR: Not reported/not retrievable; NT: Nuchal translucency; P: Para; PCOS: Polycystic ovary syndrome; T2D: Type 2 diabetes.

Table 2 Case series of human glucagon-like peptide-1 receptor agonist exposure before or during pregnancy

Ref.	Country	GLP-1RA/dose	Exposure window/cessation timing	Maternal background/metabolic profile	Delivery/birth weight	Maternal outcome	Fetal/neonatal outcome	Follow-up	Interpretation
Doğan et al[21], 2024 (case 1)	Turkey	Exenatide, dose NR	13-17 GW for approximately 4 weeks	40 years; morbid obesity, 139 kg; PCOS and T2D; BMI: > 35 kg/m2	First pregnancy: 37 weeks; delivery mode NR	Uneventful	ASD (secundum): 4 mm	ASD closed spontaneously by 3 years	Isolated ASD; high-risk metabolic substrate; later spontaneous closure
Doğan et al[21], 2024 (case 2)	Turkey	Exenatide, dose NR	3 months preconception to 13 GW	Same patient	Second pregnancy: 37.5 weeks	Uneventful	No congenital anomaly	5 years, uneventful	Same mother later had unaffected pregnancy; argues against reproducible teratogenic pattern
Banerjee and Dasgupta[22], 2026 (case 1)	India	Dulaglutide 1.5 mg/week	7 months preconception to 6-7 GW until pregnancy confirmation	26 years; PCOS, morbid obesity, OSA, hypothyroidism, T2D, MASLD; BMI: 47.9 kg/m2	NR; 2900 g	Uneventful	Healthy baby	NR	Reassuring early dulaglutide exposure in high-risk metabolic background
Banerjee and Dasgupta[22], 2026 (case 2)	India	Oral semaglutide 7 mg/day	12 months preconception to 6 GW until pregnancy confirmation	28 years; PCOS, obesity, T2D, infertility; BMI: 36.25 kg/m2	NR; 2600 g	Uneventful	Healthy baby	NR	Reassuring early semaglutide exposure; sparse follow-up
Morton and He[23], 2026 (case 1)	Australia	Semaglutide, dose NR	Preconception to 4 GW	33 years; G3P2; T2D and obesity; BMI: 35 kg/m2	LUCS, 38.3 weeks; 3910 g	Uneventful	Healthy baby	NR	Reassuring
Morton and He[23], 2026 (case 2)	Australia	Semaglutide, dose NR	Preconception to 4 GW	35 years; G1P0; T2D and obesity, BMI: 37 kg/m2; HTN, smoker, idiopathic intracranial hypertension	38.1 weeks; 3288 g	Uneventful	Cardiac anomaly, not specified	NR	Isolated unspecified cardiac anomaly with multiple maternal confounders
Morton and He[23], 2026 (case 3)	Australia	Semaglutide, dose NR	Preconception to 6 GW	37 years; G4P3; T2D, morbid obesity, BMI: 43 kg/m2; HTN	38.4 weeks; 3484 g	Uneventful	Healthy baby	NR	Reassuring
Morton and He[23], 2026 (case 4)	Australia	Semaglutide, dose NR	Preconception to 7 GW	31 years; G6P5; T2D and obesity, BMI: 40 kg/m2; Addison disease, OSA, previous neonatal death	LUCS, 35.6 weeks; 4800 g	Preterm delivery	Macrosomia, polyhydramnios, RDS	NR	Adverse metabolic/neonatal outcomes in very high-risk pregnancy
Morton and He[23], 2026 (case 5)	Australia	Semaglutide, dose NR	Preconception to 6 GW	35 years; G3P2; T2D and obesity, BMI: 30 kg/m2	Vaginal delivery, 31.6 weeks; 1035 g	Preeclampsia, preterm delivery	Fetal growth restriction	NR	Severe obstetric outcome; maternal diabetes/obesity confounding substantial
Morton and He[23], 2026 (case 6)	Australia	Semaglutide, dose NR	Preconception to 6 GW	31 years; G3P2; T2D, obesity, BMI: 40 kg/m2; PCOS	LUCS, 38.2 weeks; 3950 g	Uneventful	Macrosomia	NR	Macrosomia likely metabolic background-related
Morton and He[23], 2026 (case 7)	Australia	Semaglutide, dose NR	Preconception to 6 GW	35 years; G1P0; T2D, obesity, BMI: 30 kg/m2	36.4 weeks; 3360 g	Preterm delivery	Healthy baby	NR	Preterm but otherwise reassuring
Morton and He[23], 2026 (case 8)	Australia	Semaglutide, dose NR	Preconception to 6 GW	39 years; G3P2; T2D, overweight, BMI: 29 kg/m2	34.5 weeks; 3896 g	Preterm delivery	Fetal distress, RDS	NR	Adverse neonatal respiratory outcome; background T2D and prematurity confound interpretation
Morton and He[23], 2026 (case 9)	Australia	Semaglutide, dose NR	Preconception to 6 GW	27 years; G2P1; T2D, overweight, BMI: 29 kg/m2	36.5 weeks; 3080 g	Preterm delivery	Healthy baby	NR	Preterm but no anomaly
Morton and He[23], 2026 (case 10)	Australia	Semaglutide, dose NR	Preconception to 6 GW	26 years; G1P0; T2D, overweight, BMI: 26 kg/m2	38.1 weeks; 3348 g	Uneventful	Healthy baby	NR	Reassuring
Morton and He[23], 2026 (case 11)	Australia	Semaglutide, dose NR	Preconception to 4 GW	34 years; G1P0; T2D, obesity, BMI: 40 kg/m2	40 weeks; 3462 g	Uneventful	Healthy baby	NR	Reassuring
Morton and He[23], 2026 (case 12)	Australia	Semaglutide, dose NR	Preconception to 2 GW	33 years; G1P0; T2D, obesity, BMI: 30 kg/m2	38.3 weeks; 3852 g	Uneventful	Macrosomia	NR	Macrosomia likely diabetes/obesity-related
Morton and He[23], 2026 (case 13)	Australia	Semaglutide, dose NR	Preconception to 6 GW	35 years; G2P1; obesity, non-T2D	LUCS, 38.5 weeks; 3930 g	Uneventful	Macrosomia	NR	Reassuring for malformation; fetal size remains a metabolic issue

Detailed Joanna Briggs Institute domain-level appraisal of case series is provided in Supplementary Table 3. ASD: Atrial septal defect; BMI: Body mass index; G: Gravida; GLP-1RA: Glucagon-like peptide-1 receptor agonist; GW: Gestational week; HTN: Hypertension; LUCS: Lower uterine cesarean section; MASLD: Metabolic dysfunction-associated steatotic liver disease; NR: Not reported/not retrievable; OSA: Obstructive sleep apnea; P: Para; PCOS: Polycystic ovary syndrome; RDS: Respiratory distress syndrome; T2D: Type 2 diabetes.

Table 3 Pharmacovigilance and regulatory clinical-trial pregnancy data

Ref.	Evidence type	Data source	GLP-1RA exposure	Comparator	Exposure window/cessation timing	Maternal outcomes	Fetal/neonatal outcomes	Strength	Limitation	Interpretation
Zhou et al[24], 2025	Pharmacovigilance signal-detection study	FAERS 19-year data	354 pregnancy-related cases comprising 1671 ADR reports; liraglutide: 150; semaglutide: 106; dulaglutide: 52	FAERS comparator; sensitivity analysis using other pregnant women in FAERS	Any time during pregnancy	ROR025 signals-spontaneous abortion: 32.24, preeclampsia: 5.06, Imminent abortion: 1.40, stillbirth: 1.15	No MCM signal after sensitivity analysis using pregnant comparator	Broad real-world surveillance; multiple GLP-1RAs; used ROR and Bayesian IC; pregnancy-specific sensitivity analysis	No denominator; cannot estimate incidence or causality; reporting bias, duplicate reports, missing exposure timing, confounding by obesity/T2D/PCOS/HTN. No maternal baseline metabolic data available	Signal for spontaneous abortion and preeclampsia; hypothesis-generating, not risk-estimating
Parker et al[25], 2025	Regulatory clinical-trial inadvertent pregnancy dataset	FDA/EMA regulatory trial documents before approval	112 GLP-1RA-exposed pregnancies: Exenatide 4, lixisenatide 3, liraglutide 44, dulaglutide 7, albiglutide 6, semaglutide 41, tirzepatide 7	38 placebo/non-GLP-1RA comparator pregnancies	From pre-pregnancy reporting of incidental pregnancy and follow-up to delivery	1 preeclampsia; 1 oligohydramnios; 1 low birth weight; 1 mild gestational hypertension/cholestasis; 48 healthy live births; 24 spontaneous abortions; 3 ectopic pregnancies; 14 elective terminations; 13% elective termination in both exposed and unexposed	Healthy live birth: 43% vs 34%; MCM: 1.8% vs 5.3%; stillbirth: 0.9% vs 5.3%; spontaneous abortion: 22% vs 13%; ectopic pregnancy: 2.7% vs 7.9%; nonviable pregnancies: 25.2% exposed vs 26.3% unexposed; P = NR for any outcomes	Structured regulatory clinical trial pregnancy data; class-wide exposure across several GLP-1RAs; some comparator pregnancies available	Pregnancy was an exclusion criterion; post hoc extraction; small numbers; incomplete outcomes; no adjustment for maternal baseline risk; not a conventional cohort	Reassuring against a large teratogenic signal, but should be interpreted as intermediate evidence, not definitive safety evidence

Design-adapted appraisal of the pharmacovigilance and regulatory clinical-trial pregnancy evidence is provided in Supplementary Table 5. ADR: Adverse drug reaction; EMA: European Medicines Agency; FAERS: United States Food and Drug Administration Adverse Event Reporting System; FDA: Food and Drug Administration; GLP-1RA: Glucagon-like peptide-1 receptor agonist; HTN: Hypertension; MCM: Major congenital malformation; NR: Not reported/not retrievable; PCOS: Polycystic ovary syndrome; ROR: Reporting odds ratio; ROR025: Lower limit of the 95% confidence interval of reporting odds ratio; T2D: Type 2 diabetes.

Table 4 Diabetes-specific comparative cohort and registry studies

Ref.	Country/design	Exposed population	GLP-1RA	Exposure window/cessation timing	Comparator	Maternal outcomes	Fetal/neonatal outcomes	Strength	Limitation	Interpretation
Chou et al[26], 2026	Taiwan (China); T2D cohort	160 T2D; 19 obese among exposed	Not specified	90 days before through 90 days after LMP	606 PM T2D cohort on insulin	Preterm 34.6% vs 31.9%; P = NS	MCM: 0.6% vs 0.2%; stillbirth: 4.4% vs 2.1%; SGA: 2.6% vs 3%; all P = NS	Diabetes-specific active comparator; PM T2D cohort	Small exposed sample; agent unspecified; limited power for rare anomalies	Reassuring; risk not greater than insulin-exposed T2D pregnancies
Cesta et al[27], 2024	Nordic countries/United States/Israel; T2D cohort	938 T2D; 483 obese among exposed	Not specified	180-365 days before LMP to end of first trimester (90-97 days)	5078 T2D on insulin	NR	MCM: 8.2% vs 7.8%; cardiac anomalies: 3.2% vs 4.2%; all P = NS. First-trimester GLP-1RA: MCM: 6.7% vs 7.8%; cardiac anomalies: 1.6% vs 4.2%. All P = NS	Large multinational population-based dataset; clinically relevant diabetic comparator	Prescription-based exposure; limited glycemic/BMI details; maternal outcomes not central	Reassuring for major teratogenicity compared with insulin-treated diabetes
Hanif et al[28], 2025	United States; T2D cohort	1826 T2D	Not specified	1 year before to 1 month after first trimester pregnancy diagnosis	1826 T2D unexposed to GLP-1RA (mostly LSM and/or insulin)	Maternal all-cause mortality, gestational HTN, preeclampsia/eclampsia: All P = NS	Cardiac anomaly, kidney anomaly: All P = NS	Large PM T2D cohort	Fetal assessment limited to cardiac and kidney anomalies. Agent unspecified; broad exposure window; residual confounding	Reassuring; no increased risk compared with T2D controls
Lewin et al[29], 2026	United States; T2D cohort, 3-year data	35083 DM; (T2D: 34343; T1D: 740)	Not specified	Any time during pregnancy for any duration	108510 DM; (T2D: 98628; T1D: 9882) not on GLP-1RA	PET 13.1% vs 11.9%, P < 0.0001; preterm 23.1% vs 20.8%, P < 0.0001; CD: 44.4% vs 38.9%, P < 0.0001	First-trimester abortion/termination 9.8% vs 7.5%, P < 0.0001; MCM: 3.3% vs 3.3%, P = 0.63; genital malformations: 0.7% vs 0.6%, P = 0.02; urinary malformations: 0.5% vs 0.4%, P = 0.01	Very large sample; able to detect rare system-specific signals	More severe baseline cohort; possible T1D admixture; strong confounding by disease severity; broad exposure definition	Reassuring for overall MCM but signals for PET, preterm, cesarean, abortion/termination, genital and urinary anomalies require cautious evaluation

Detailed Joanna Briggs Institute domain-level appraisal of the cohort, registry, and controlled human studies is provided in Supplementary Table 4. BMI: Body mass index; CD: Cesarean delivery; DM: Diabetes mellitus; GLP-1RA: Glucagon-like peptide-1 receptor agonist; HTN: Hypertension; LMP: Last menstrual period; LSM: Lifestyle modification; MCM: Major congenital malformation; NR: Not reported/not retrievable; NS: Not significant; PET: Preeclampsia; PM: Propensity-matched; SGA: Small for gestational age; T1D: Type 1 diabetes; T2D: Type 2 diabetes.

Table 5 Obesity-, polycystic ovary syndrome-, and fertility-focused cohorts and registry studies

Ref.	Country/design	Exposed population	GLP-1RA	Exposure window/cessation timing	Comparator	Maternal outcomes	Fetal/neonatal outcomes	Strength	Limitation	Interpretation
Bolek et al[30], 2026	Slovakia; prospective cohort	20 obese + PCOS + prediabetes	Semaglutide	Stopped ≥ 30 days before pregnancy	NR	Live birth 12/20 (60%); no reported maternal complication	Eutrophic neonates	Prospective; semaglutide-specific	Very small; no comparator; preconception discontinuation	Reassuring but not informative for continued pregnancy exposure
Bartelt et al[33], 2024	United States; retrospective cohort, 7-year data	1208 obese	Not specified	90 days before conception to during pregnancy	Unexposed general population, n = 775478	Preterm birth signal: 13% vs 10%	Higher NICU admission: 12% vs 8%	Large real-world cohort	General population comparator; high risk of confounding by obesity/metabolic disease	Not reassuring with general comparator. CHD and failure-to-thrive rates were similar by exposure timing; needs obesity-matched controls
Guo et al[31], 2025	China; retrospective obese non-T2D cohort	20 obese after exclusion of T2D	Semaglutide, titrated up to 2.4 mg/week	Used for 6 months; stopped 2 months before conception	22 obese treated with LSM	GDM 20% vs 31.8%; CD similar; GWG: 9.16 kg vs 17.7 kg, P < 0.05	No MCM; no NICU admission; no neonatal hypoglycemia; similar birth weight	Obesity comparator; T2D excluded; dose specified	Very small human study; preconception exposure only. Mostly animal/mechanistic emphasized study	Suggests improved GWG and GDM after preconception semaglutide; reassuring but underpowered
Li et al[32], 2022	China; controlled preconception PCOS study	57 overweight/obese, infertility, PCOS	Exenatide	12-week pregestational exenatide	Obese PCOS/prediabetes; n = 60 on metformin	Spontaneous pregnancy rate by week 24: 29.2% vs 14.7%; total pregnancy by week 64: 79.2% vs 76%; pregnancy outcomes not significantly different	Miscarriage, live birth, preterm birth, GDM, gestational hypertension, macrosomia and birthweight not significantly different; one ASD reported in exenatide arm	Active comparator; preconception fertility context	Not designed as pregnancy-safety study; GLP-1RA was not continued as assigned therapy during organogenesis; metformin co-use and fertility-care surveillance confound interpretation	Early reassuring signal for preconception exenatide in PCOS

Detailed Joanna Briggs Institute domain-level appraisal of the cohort, registry, and controlled human studies is provided in Supplementary Table 4. ASD: Atrial septal defect; CD: Cesarean delivery; CHD: Congenital heart disease; GDM: Gestational diabetes mellitus; GLP-1RA: Glucagon-like peptide-1 receptor agonist; GWG: Gestational weight gain; LSM: Lifestyle modification; MCM: Major congenital malformation; NICU: Neonatal intensive care unit; NR: Not reported/not retrievable; PCOS: Polycystic ovary syndrome; T2D: Type 2 diabetes.

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.

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.