GLP-1 Receptor Agonists Should Not Be Used During Pregnancy
GLP-1 receptor agonists are contraindicated during pregnancy due to potential risks to the fetus, including embryonic death, structural abnormalities, and growth alterations observed in animal studies. 1, 2
Safety Evidence and Concerns
- FDA labeling for semaglutide (Ozempic) explicitly states that it should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, with animal studies showing embryofetal mortality and structural abnormalities at doses below the maximum recommended human dose 1
- Similarly, liraglutide (Victoza) FDA labeling indicates potential risks to the fetus based on animal reproduction studies, with increased early embryonic deaths and fetal abnormalities observed at clinical exposures 2
- All antiobesity medications, including GLP-1 receptor agonists, should not be used during pregnancy or lactation according to current guidelines 3
- A 2025 systematic review found evidence for adverse offspring effects of GLP-1 agonists in both animal and limited human studies 4
Animal Study Findings
- In pregnant rats administered semaglutide during organogenesis, embryofetal mortality, structural abnormalities, and growth alterations occurred at maternal exposures below the maximum recommended human dose 1
- In rabbits and monkeys, semaglutide was associated with early pregnancy losses and structural abnormalities 1
- Liraglutide exposure in pregnant rats was associated with early embryonic deaths and fetal abnormalities including irregular ossification of the skull and kidney/blood vessel abnormalities 2
- In pregnant rabbits, liraglutide decreased fetal weight and dose-dependently increased the incidence of major fetal abnormalities 2
Human Data Limitations
- There is a significant lack of controlled human studies on GLP-1 receptor agonist use during pregnancy 5, 6
- Available human data comes primarily from unplanned pregnancies during clinical trials, which is insufficient to establish safety 5
- A recent review concluded there is not enough evidence to predict any adverse effects, or lack thereof, from periconceptional exposure to GLP-1 receptor agonists 6
- Women of reproductive age should be counseled on effective contraception while taking these medications 3, 6
Recommendations for Clinical Practice
- GLP-1 receptor agonists should be discontinued as soon as pregnancy is confirmed 5, 4
- Women of reproductive age should use effective contraception while on GLP-1 receptor agonists 3, 6
- GLP-1 receptor agonists can decrease the effectiveness of oral contraceptives due to delayed gastric emptying; addition of barrier methods is recommended for 4 weeks after initiation and after each dose increase 3
- The use of GLP-1 receptor agonists for weight management is specifically not recommended in pregnancy due to potential adverse fetal outcomes 3
Special Considerations
- For women with diabetes who become pregnant while on GLP-1 receptor agonists, alternative diabetes treatments with established safety profiles during pregnancy should be considered 3
- Metformin is used to improve fertility and recommended by the American College of Obstetricians and Gynecologists as a second-line medication for diabetes during pregnancy 3
- The establishment of patient registries to capture data on GLP-1 receptor agonist exposure during pregnancy is a high priority to address current knowledge gaps 5
In conclusion, based on the available evidence, particularly FDA drug labeling and animal studies showing significant risks, GLP-1 receptor agonists should not be used during pregnancy. The potential risks to fetal development outweigh the benefits for weight management or glycemic control during pregnancy.