GLP-1 Receptor Agonists Should Not Be Used During Pregnancy
GLP-1 receptor agonists are contraindicated during pregnancy and should be discontinued immediately upon pregnancy recognition. 1 Current guidelines explicitly state that all antiobesity medications, including GLP-1 receptor agonists, should not be used during pregnancy or lactation. 1
Guideline-Based Recommendations
Contraception Requirements
- Women of reproductive age must use effective contraception while taking GLP-1 receptor agonists 1
- Barrier methods should be added for 4 weeks after initiation and after each dose increase because GLP-1 receptor agonists can decrease oral contraceptive effectiveness through delayed gastric emptying 1
Management Upon Pregnancy Recognition
- Stop GLP-1 receptor agonists immediately when pregnancy is confirmed 2
- For women with diabetes, transition to insulin as the preferred medication for treating hyperglycemia in pregnancy 3
- Metformin is recommended by the American College of Obstetricians and Gynecologists as a second-line medication for diabetes during pregnancy 1
Evidence on Safety Profile
Animal Studies Show Concerning Effects
- Animal studies demonstrate adverse outcomes including decreased fetal growth, skeletal and visceral anomalies, and embryonic death 4
- Reduced fetal weight, delayed ossification, and skeletal variants have been observed in animal models 5
Limited Human Data
The available human evidence is reassuring but insufficient:
- A large observational study of 938 pregnancies with type 2 diabetes found no significantly increased risk of major congenital malformations comparing GLP-1 receptor agonists to insulin 4
- However, this study lacked critical information on maternal glycemic control and diabetic fetopathy, making definitive conclusions impossible 4
- The incidence of congenital abnormalities appears relatively low in inadvertent exposures during clinical trials 2
- Case reports include one instance of atrial septal defect in an infant exposed to exenatide during the first trimester, though the child's defect spontaneously closed by age 3 6
Critical Knowledge Gaps
- No prospective studies in humans exist 4
- Evidence on fetal growth restriction, embryonic/fetal death, and other complications is lacking 4
- All available human data comes from unplanned pregnancies during clinical trials, not planned exposures 2
FDA Classification
The FDA label for exenatide states: "Use during pregnancy only if the potential benefit justifies the risk to the fetus" 7, which in practical terms means avoid use given safer alternatives exist.
Clinical Pitfalls to Avoid
Do not continue GLP-1 receptor agonists during pregnancy based on inadequate evidence. The absence of a clear pattern of malformations does not equal proof of safety, particularly when:
- Diabetic embryopathy is directly related to maternal hyperglycemia degree 4
- Most studies lack data on maternal glycemic control during exposure 4
- Long-term pediatric outcomes remain unknown 4
Do not assume weight loss benefits outweigh unknown fetal risks. The use of GLP-1 receptor agonists specifically for weight management is not recommended in pregnancy due to potential adverse fetal outcomes. 1
Counseling Patients on Inadvertent Exposure
If a patient becomes pregnant while taking a GLP-1 receptor agonist:
- Discontinue the medication immediately 2
- Counsel that there is insufficient evidence to predict adverse effects or their absence 4
- Arrange appropriate prenatal monitoring and diabetes management with insulin or metformin 3, 1
- Document the exposure in pregnancy registries when available to contribute to future knowledge 2