Effects of GLP-1 agonists and SGLT2 inhibitors during pregnancy and lactation on offspring outcomes: a systematic review of the evidence.

Muller DRP, Stenvers DJ, Malekzadeh A, Holleman F, Painter RC, Siegelaar SE

Frontiers in endocrinology10 Oct 2023Cited by 122 (Europe PMC)

PMID37881498PMCIDPMC10597691DOI10.3389/fendo.2023.1215356PepBankPUB-37881498

Summary

Aims/hypothesisGlucagon-like peptide 1 (GLP-1) agonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors are novel drugs which have recently seen rapid uptake in the treatment of type 2 diabetes and obesity. The paucity of data regarding their safety during pregnancy and lactation causes a dilemma for the physician. The aim of the present study was to systematically review all available data on the offspring effects of GLP-1 agonists and SGLT2 inhibitors during pregnancy and lactation.MethodsWe systematically searched PubMed, clinicaltrials.gov, FDA and EMA product information on GLP-1 agonists and SGLT2 inhibitors in pregnancy and lactation from inception up to 19 April 2022 without language restrictions. We approached both the Netherlands Pharmacovigilance Centre Lareb on January 17^th 2023 and the Teratology Information Service (TIS) of Switzerland on February 6^th 2023. Eligible studies investigating the safety (including congenital anomalies, fetal growth, perinatal demise) in animals or humans, or reporting the degree of transfer of these drugs to the fetus, breast milk or breastfed neonate. Two reviewers independently assessed and selected studies for inclusion and subsequently resolved discrepancies by discussion.ResultsWe included 39 records (n=9 theoretical; based on drug properties, n=7 human; n=23 animal, including 76 human offspring, and an unknown number of animal offspring as these numbers could not be retrieved from the FDA and EMA product information). In animal studies, GLP1-agonists were associated with reduced fetal weight and/or growth, delayed ossification and skeletal variants, usually associated with a reduction in maternal weight gain and decreased food consumption. Exendin-4 (GLP1-agonist) was not transported across the maternal-fetal placental interface. In human studies, exenatide (GLP1-agonist) showed a fetal-to-maternal peptide concentration ratio of ≤ 0.017 in ex vivo human placental perfusion in a single placenta. Liraglutide (GLP1-agonist) showed no significant maternal to fetal transfer at least 3.5 hours after maternal exposure in a human study with one subject. In animal studies, GLP-1 agonists were excreted in breast milk; human data on excretion were not available. In animal studies, SGLT2 inhibitors were generally safe during the first trimester but exposure during postnatal day 21 to 90 in juvenile rats, a period coinciding with the late second and third trimester of human renal development, caused dilatation of the renal pelvis and tubules. Human data consisted of a pharmaceutical database of inadvertent pregnancies during SGLT2 inhibitor use, which found an increase in miscarriages and congenital malformations. In animal studies SGLT2 inhibitors were excreted in breast milk and affected neonatal growth, but human data are not available.Conclusion/interpretationWe found evidence for adverse offspring effects of GLP-1 agonists and SGLT2 inhibitors also in human studies. Our findings broadly support the advice to discontinue GLP-1 agonists and SGLT2 inhibitors during pregnancy and lactation, and also support the ongoing registration of pregnancy outcomes in pharmacological databases since the amount of available data is scarce and mostly limited to animal studies.Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=219877.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

1 result from studies that gave the peptide. 1 result from people.

01HumanSystematic reviewPharmacokinetics
In a human study with one subject, liraglutide showed no significant maternal-to-fetal transfer at least 3.5 hours after maternal exposure.
In plain wordsA human study of one subject found no significant transfer of liraglutide from mother to fetus at least 3.5 hours after exposure.
Peptide
Liraglutide
Outcome
No significant changeMaternal-to-fetal transfer of liraglutide
Study
n = 1
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
Dose not stated
Source sentences
Summary
Liraglutide (GLP1-agonist) showed no significant maternal to fetal transfer at least 3.5 hours after maternal exposure in a human study with one subject.
1 context sentence(design, population, supporting numbers)
Summary · context
We included 39 records (n=9 theoretical; based on drug properties, n=7 human; n=23 animal, including 76 human offspring, and an unknown number of animal offspring as these numbers could not be retrieved from the FDA and EMA product information).
Show in the study text Report a problemFND-3788149801

Studies that did not test the peptide alone4

In this study, Liraglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Liraglutide.

02AnimalNot a test of Liraglutide aloneAnimal study (in vivo)Safety outcome
In animal studies reviewed, GLP-1 agonists as a class were associated with reduced fetal weight and growth.
In plain wordsIn animal studies, GLP-1 drugs as a group were linked to lower fetal weight and growth.
Peptide
Liraglutide
Outcome
DecreaseFetal weight and growth
Study
n: not reported in source
Outcome group
Adverse events · Reproductive and sexual health
Source sentences
Summary
GLP1-agonists were associated with reduced fetal weight and/or growth
1 context sentence(design, population, supporting numbers)
Summary · context
We included 39 records (n=9 theoretical; based on drug properties, n=7 human; n=23 animal, including 76 human offspring, and an unknown number of animal offspring as these numbers could not be retrieved from the FDA and EMA product information).
In this study, Liraglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Liraglutide.
Show in the study text Report a problemFND-3788149802
03AnimalNot a test of Liraglutide aloneAnimal study (in vivo)Safety outcome
In animal studies reviewed, GLP-1 agonists as a class were associated with delayed ossification and skeletal variants.
In plain wordsIn animal studies, GLP-1 drugs as a group were linked to delayed bone formation and skeletal variants.
Peptide
Liraglutide
Outcome
MixedOssification and skeletal variants
Study
n: not reported in source
Outcome group
Adverse events · Reproductive and sexual health
Source sentences
Summary
GLP1-agonists were associated with reduced fetal weight and/or growth, delayed ossification and skeletal variants
1 context sentence(design, population, supporting numbers)
Summary · context
We included 39 records (n=9 theoretical; based on drug properties, n=7 human; n=23 animal, including 76 human offspring, and an unknown number of animal offspring as these numbers could not be retrieved from the FDA and EMA product information).
In this study, Liraglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Liraglutide.
Show in the study text Report a problemFND-3788149803
04AnimalNot a test of Liraglutide aloneAnimal study (in vivo)Other
In animal studies reviewed, fetal effects of GLP-1 agonists as a class were usually associated with a reduction in maternal weight gain and decreased food consumption.
In plain wordsIn animal studies, fetal effects of GLP-1 drugs as a group usually came with lower maternal weight gain and less food eaten.
Peptide
Liraglutide
Outcome
DecreaseMaternal weight gain and food consumption
Study
n: not reported in source
Outcome group
Body weight · Metabolic and weight
Source sentences
Summary
usually associated with a reduction in maternal weight gain and decreased food consumption.
1 context sentence(design, population, supporting numbers)
Summary · context
We included 39 records (n=9 theoretical; based on drug properties, n=7 human; n=23 animal, including 76 human offspring, and an unknown number of animal offspring as these numbers could not be retrieved from the FDA and EMA product information).
In this study, Liraglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Liraglutide.
Show in the study text Report a problemFND-3788149804
05AnimalNot a test of Liraglutide aloneAnimal study (in vivo)Pharmacokinetics
In animal studies reviewed, GLP-1 agonists as a class were excreted in breast milk.
In plain wordsIn animal studies, GLP-1 drugs as a group passed into breast milk.
Peptide
Liraglutide
Outcome
Not applicableExcretion in breast milk
Study
n: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Source sentences
Summary
In animal studies, GLP-1 agonists were excreted in breast milk
1 context sentence(design, population, supporting numbers)
Summary · context
We included 39 records (n=9 theoretical; based on drug properties, n=7 human; n=23 animal, including 76 human offspring, and an unknown number of animal offspring as these numbers could not be retrieved from the FDA and EMA product information).
In this study, Liraglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Liraglutide.
Show in the study text Report a problemFND-3788149805

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
12 Oct 2026, 11:11 UTC
Study results updated
Version 1
9 Oct 2026, 03:05 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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