Glucagon-like peptide-1 receptor agonists (GLP1RAs) are used to treat diabetes, obesity, and polycystic ovarian syndrome (PCOS)
Semaglutide, liraglutide, lixisenatide, dulaglutide, and tirzepatide are the current GLP1RAs available in Canada. These are approved for the treatment of type 2 diabetes and obesity and have been used as off-label treatment for PCOS. Systematic reviews suggest that GLP1RAs can improve the spontaneous pregnancy rate, menstrual cyclicity, insulin sensitivity, and anthropometric outcomes (e.g., body mass index, weight) among patients with PCOS.1,2
Patients should stop taking GLP1RAs 1–2 months before a planned pregnancy
Preclinical animal studies have shown teratogenicity at doses similar to those used in humans.3 Offspring of pregnant animals exposed to GLP1RAs have shown skeletal abnormalities and reductions in fetal weight and growth. Clinicians should counsel patients to use contraception while taking GLP1RAs. Expert opinion advises that patients stop GLP1RAs before pregnancy (Appendix 1, available at www.cmaj.ca/lookup/doi/10.1503/cmaj.240768/tab-related-content).
No association between GLP1RAs and congenital malformations has been shown in humans
Data are limited. Two small observational studies suggest no increased risk of major congenital malformations among infants born to females exposed to GLP1RAs (n = 168; n = 938) in early pregnancy or before conception.4,5
Withdrawal of GLP1RAs can lead to rebound weight gain
Stopping GLP1RAs can lead to regaining around two-thirds of previous weight loss within a year.6 Obesity is associated with adverse pregnancy outcomes including gestational diabetes, hypertensive disorders, and pregnancy loss. Patients should work with their health care providers to strive for optimal weight before pregnancy and appropriate gestational weight gain.
Lactating patients should avoid taking GLP1RAs
Given that GLP1RAs are large protein molecules, they are unlikely to transfer to breast milk in high concentrations (Appendix 1). Any amount ingested via breast milk is likely to be degraded by proteases in the child’s stomach. However, given a paucity of human data on their safety during lactation, experts suggest that GLP1RAs should be avoided while breastfeeding.
Supplementary Information
Acknowledgement
The authors thank Dr. Don Redelmeier for helpful comments on earlier versions of the manuscript.
Footnotes
Competing interests: Jonathan Zipursky and Tali Bogler are medical advisors for First Exposure; Cynthia Maxwell is the medical director. Jonathan Zipursky reports payments from law firms for medicolegal opinions on the safety and effectiveness of drugs unrelated to the current work. No other competing interests were declared.
This article has been peer reviewed.
References
- 1.Goldberg A, Graca S, Liu J, et al. Anti-obesity pharmacological agents for polycystic ovary syndrome: a systematic review and meta-analysis to inform the 2023 international evidence-based guideline. Obes Rev 2024;25:e13704. [DOI] [PubMed] [Google Scholar]
- 2.Zhou L, Qu H, Yang L, et al. Effects of GLP1RAs on pregnancy rate and menstrual cyclicity in women with polycystic ovary syndrome: a meta-analysis and systematic review. BMC Endocr Disord 2023;23:245. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Muller DRP, Stenvers DJ, Malekzadeh A, et al. Effects of GLP-1 agonists and SGLT2 inhibitors during pregnancy and lactation on offspring outcomes: a systematic review of the evidence. Front Endocrinol (Lausanne) 2023;14:1215356. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Dao K, Shechtman S, Weber-Schoendorfer C, et al. Use of GLP1 receptor agonists in early pregnancy and reproductive safety: a multicentre, observational, prospective cohort study based on the databases of six Teratology Information Services. BMJ Open 2024;14:e083550. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Cesta CE, Rotem R, Bateman BT, et al. Safety of GLP-1 receptor agonists and other second-line antidiabetics in early pregnancy. JAMA Intern Med 2024;184:144–52. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Wilding JPH, Batterham RL, Davies M, et al.; STEP 1 Study Group. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP1 trial extension. Diabetes Obes Metab 2022;24:1553–64. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.